Oral mucosal delivery system and preparation method and application thereof

Abstract

The present application relates to an oral mucosal delivery system and a preparation method and application thereof. The oral mucosal delivery system comprises a polymer skeleton, wherein the polymer skeleton is formed by polyvinyl pyrrolidone and gallic acid, and the mass ratio of the polyvinyl pyrrolidone to gallic acid is (1-3):1. The oral mucosal delivery system has strong adhesion to the oral mucosa and can be easily removed.

Description

Technical Field

[0001] The present application relates to the technical field of drug delivery, and in particular to an oral mucosal delivery system and a preparation method and application thereof. Background Art

[0002] In the clinical treatment of diseases, oral mucosal administration is one of the multiple routes of administration. When administering drugs through the oral mucosa, the drug can directly enter the blood circulation through the mucosa, which can avoid the degradation and loss of oral drugs in the stomach and the first-pass effect of the liver. Therefore, oral mucosal administration can quickly increase the drug concentration in the blood and accelerate the treatment effect.

[0003] There are many oral mucosal drug delivery dosage forms, including tablets, films, patches, gels, ointments, and nanoparticles. However, due to the high humidity and dynamic environment of the oral cavity, traditional oral mucosal drug delivery dosage forms are difficult to adhere to the oral mucosa for a long time, and thus difficult to provide stable drug delivery or easy to diffuse throughout the oral cavity, increasing the possibility of being swallowed into the gastrointestinal tract, resulting in the loss of active ingredients. Summary of the invention

[0004] Based on this, the present application provides an oral mucosal delivery system that has strong adhesion to the oral mucosa and can be easily removed, as well as a preparation method and application thereof.

[0005] In a first aspect of the present application, an oral mucosal delivery system is provided, comprising a polymer skeleton, wherein the polymer skeleton is formed by polyvinyl pyrrolidone and gallic acid, and the mass ratio of polyvinyl pyrrolidone to gallic acid is (1-3):1.

[0006] In one embodiment, the mass ratio of polyvinyl pyrrolidone to gallic acid is (1-2.5):1.

[0007] In one embodiment, the mass ratio of polyvinyl pyrrolidone to gallic acid is (1.5-2.5):1.

[0008] In one embodiment, the oral mucosal delivery system has one or more of the following features:

[0009] (1) The adhesion force is greater than or equal to 40 kPa, and optionally, the adhesion force is greater than or equal to 100 Pa;

[0010] (2) When immersed in an alkaline aqueous solution, the adhesion decreases with the immersion time.

[0011] The second aspect of the present application provides a method for preparing the oral mucosal delivery system according to the first aspect, comprising the following steps:

[0012] preparing the polyvinyl pyrrolidone and the gallic acid into a first solution and a second solution respectively;

[0013] The first solution and the second solution are mixed, stirred, and the precipitated precipitate is collected and dried to prepare the oral mucosal delivery system.

[0014] In one embodiment, in the first solution, the mass percentage of polyvinyl pyrrolidone is 8% to 12%.

[0015] In one embodiment, the mass percentage of gallic acid in the second solution is 3% to 7%.

[0016] The third aspect of the present application provides a pharmaceutical preparation, comprising the oral mucosal delivery system of the first aspect and an active ingredient loaded in the oral mucosal delivery system.

[0017] In one embodiment, the active ingredient is glucose.

[0018] The fourth aspect of the present application provides use of the oral mucosal delivery system described in the first aspect or the drug preparation described in the third aspect in the preparation of a drug for treating or preventing neonatal hypoglycemia.

[0019] The oral mucosal delivery system uses polyvinylpyrrolidone (PVP) and gallic acid (GA) in a specific ratio as the polymer skeleton. There are tertiary amide groups and carbonyl groups in PVP, and hydroxyl groups and carboxyl groups in GA. When PVP and GA are mixed, a PVP / GA composite material (film) can be quickly formed between the two through strong hydrogen bonds, and under the moist environment of the oral mucosa, hydrogen bonds can be formed with the oral mucosa, and water can be absorbed in situ to form a hydrogel to achieve the purpose of adhesion, and the degree of adhesion is high, and it can still firmly adhere to the oral mucosa, especially the tongue mucosa, even in the case of water flushing. At the same time, the oral mucosal delivery system also has reversible adhesion properties, and the firmly adhered oral mucosal delivery system can be removed by using, for example, an alkaline aqueous solution, without damaging biological tissues.

[0020] In addition, it was found during the research process that the above oral mucosal delivery system also has the following advantages:

[0021] (1) The conventional oral mucosal administration dosage form has the problem of uneven distribution of glucose and is difficult to stably increase blood sugar. The oral mucosal delivery system of the present application has an even distribution of active ingredients and has a drug sustained release capability, which can continuously release active ingredients such as glucose, thereby achieving the purpose of stably increasing blood sugar.

[0022] (2) It has excellent cell and in vivo biocompatibility, is non-toxic and harmless to the oral mucosa, and can be used in newborns. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is a Fourier transform infrared spectroscopy characterization spectrum of the PVP / GA film prepared in Example 1;

[0024] Figure 2 It is a comparison chart of the adhesion performance test results of the PVP / GA films prepared in Examples 1 to 4 and Comparative Example 1;

[0025] Figure 3 Schematic diagram of washing the PVP / GA film prepared in Example 1 with water;

[0026] Figure 4 The curve showing the change of adhesion of the PVP / GA film prepared in Example 1 in a NaHCO3 aqueous solution over time;

[0027] Figure 5 This is a demonstration diagram of the peeling of the PVP / GA film prepared in Example 1 after being treated with a NaHCO3 aqueous solution;

[0028] Figure 6 PVP / GA film containing glucose (PVP / GA (glucose) film) and commercial glucose gel Glutose15 TM (Glutose 15 TM )'s in vitro glucose release curve;

[0029] Figure 7 PVP / GA film containing glucose (PVP / GA (glucose)) and commercial glucose gel Glutose15 TM (Glutose 15 TM )'s glucose release curve in rabbits;

[0030] Figure 8 PVP / GA film loaded with glucose (PVP / GA group) and commercial glucose gel Glutose 15 TM (commercial gel group) distribution of glucose fitc in the sublingual tissue of rabbits;

[0031] Fig. 9 HOK cytotoxicity test of the PVP / GA film prepared in Example 1;

[0032] Fig.10 The biocompatibility test results of the PVP / GA film prepared in Example 1. DETAILED DESCRIPTION

[0033] The oral mucosal delivery system of the present application and its preparation method and application are further described in detail below in conjunction with specific examples. The present application can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present application more thorough and comprehensive.

[0034] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application.

[0035] The optional scope of the terms "and / or", "or / and", and "and / or" used in this article includes any one of two or more related listed items, and also includes any and all combinations of the related listed items, said any and all combinations include any combination of any two related listed items, any more related listed items, or all related listed items.

[0036] As used herein, "one or more" refers to any one, any two, or any two or more of the listed items.

[0037] In this application, "first aspect", "second aspect", "third aspect", "fourth aspect", etc. are used only for descriptive purposes and cannot be understood as indicating or implying relative importance or quantity, nor can they be understood as implicitly indicating the importance or quantity of the indicated technical features. Moreover, "first", "second", "third", "fourth", etc. only serve the purpose of non-exhaustive enumeration and description, and it should be understood that they do not constitute a closed limitation on quantity.

[0038] In the present application, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0039] In this application, when it comes to numerical ranges, unless otherwise specified, the above numerical ranges are deemed to be continuous and include the minimum and maximum values ​​of the range, as well as each value between such minimum and maximum values. Further, when a range refers to an integer, each integer between the minimum and maximum values ​​of the range is included. In addition, when multiple ranges are provided to describe features or characteristics, the ranges can be merged. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges included therein.

[0040] The percentage contents involved in this application, unless otherwise specified, refer to mass percentage for solid-liquid mixing and solid-solid mixing, and refer to volume percentage for liquid-liquid mixing.

[0041] The percentage concentrations mentioned in this application, unless otherwise specified, refer to the final concentration, which refers to the percentage of the added component in the system after the addition of the component.

[0042] The temperature parameters in this application, unless otherwise specified, allow for both constant temperature treatment and treatment within a certain temperature range. The constant temperature treatment allows the temperature to fluctuate within the accuracy range of instrument control.

[0043] The room temperature in the present application generally refers to 4°C to 30°C, preferably 20±5°C.

[0044] In a first aspect of the present application, an oral mucosal delivery system is provided, comprising a polymer skeleton, wherein the polymer skeleton is formed by polyvinyl pyrrolidone and gallic acid, and the mass ratio of polyvinyl pyrrolidone to gallic acid is (1-3):1.

[0045] Without limitation, polyvinyl pyrrolidone and gallic acid are connected by hydrogen bonds, and the structure is shown below (n represents a polymer of polyvinyl pyrrolidone, usually, the average molecular weight is usually 1300000, the group molecular weight is 111, and the degree of polymerization n is 11711):

[0046]

[0047] Specifically, reasonable control of the mass ratio of polyvinyl pyrrolidone to gallic acid can optimize the adhesion performance of the oral mucosal delivery system to the oral mucosa. Without limitation, the mass ratio of polyvinyl pyrrolidone to gallic acid includes, but is not limited to, 1:1, 1.5:1, 2:1, 2.5:1, 3:1, or a range between any two of the foregoing.

[0048] In some of the examples, the mass ratio of polyvinyl pyrrolidone to gallic acid is (1-2.5):1.

[0049] In some of the examples, the mass ratio of polyvinyl pyrrolidone to gallic acid is (1.5-2.5):1.

[0050] In some examples, the adhesion of the oral mucosal delivery system is greater than or equal to 40 kPa. Specifically, the adhesion includes, but is not limited to, 40 kPa, 45 kPa, 50 kPa, 55 kPa, 60 kPa, 65 kPa, 70 kPa, 75 kPa, 80 kPa, 85 kPa, 90 kPa, 95 kPa, 100 kPa, 105 kPa, 110 kPa, 115 kPa, 120 kPa, 125 kPa, 130 kPa, 135 kPa, 140 kPa, 145 kPa, 150 kPa. In some examples, the adhesion of the oral mucosal delivery system is greater than or equal to 100 Pa.

[0051] In some examples, the oral mucosal delivery system is immersed in an alkaline aqueous solution, and the adhesion decreases with the immersion time. Without limitation, the alkaline aqueous solution is a weak alkaline aqueous solution, such as a sodium carbonate aqueous solution, a sodium bicarbonate aqueous solution, and the like.

[0052] In some examples of the present application, a method for preparing the oral mucosal delivery system as described above is also provided, comprising the following steps:

[0053] The polyvinyl pyrrolidone and the gallic acid are respectively prepared into a first solution and a second solution, and the first solution and the second solution are solvents;

[0054] The first solution and the second solution are mixed, stirred, and the precipitated precipitate is collected and dried to prepare the oral mucosal delivery system.

[0055] Without limitation, the solvents in the first solution and the second solution may be one or both of water and ethanol.

[0056] In some examples, the mass percentage of polyvinyl pyrrolidone in the first solution is 8% to 12%. Specifically, the mass percentage of polyvinyl pyrrolidone includes but is not limited to: 8%, 8.5%, 9%, 9.5%, 10%, 10.5%, 11%, 11.5%, 12% or a range between any two of the foregoing.

[0057] In some examples, the mass percentage of gallic acid in the second solution is 3% to 7%. Specifically, the mass percentage of gallic acid includes but is not limited to: 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7% or a range between any two of the foregoing.

[0058] Some other examples of the present application further provide a pharmaceutical preparation, comprising the oral mucosal delivery system as described above and an active ingredient loaded in the oral mucosal delivery system.

[0059] In some examples, the active ingredient is glucose. In addition, without limitation, for adult medication, further options include insulin, fentanyl, and alfentanil.

[0060] Some other examples of the present application also provide use of the oral mucosal delivery system as described above or the drug preparation as described above in the preparation of a drug for treating or preventing neonatal hypoglycemia.

[0061] Neonatal hypoglycemia (NH) is a common disease that requires emergency treatment during the perinatal period. Some newborns will experience hypoglycemia within 48 hours after birth. The incidence rate is as high as 50% in newborns with high-risk factors (premature birth, maternal diabetes or obesity). Hypoglycemia can cause an immediate energy shortage in the developing newborn, especially insufficient energy supply to the brain. If not intervened as soon as possible, severe and persistent hypoglycemia can lead to irreversible brain damage and poor neurodevelopment, which will bring great burden to the family and society. Rapid correction of hypoglycemia can be achieved by providing glucose, such as through enhanced feeding, intravenous infusion of glucose, oral glucose solution, etc. In 2013, Harris et al. proved that the use of 40% glucose gel buccal mucosa can effectively increase blood sugar. Guidelines in countries such as the United States, Sweden, the United Kingdom, and Canada all recommend the use of glucose gel buccal mucosa as an initial treatment plan. However, the existing glucose gels on the market are all adult diabetes care products, and there is no glucose gel that meets the standards for use in newborns. These glucose gels contain various thickeners, flavors, and preservatives. One of the thickeners, xanthan gum, has been reported to be associated with neonatal necrotizing enterocolitis.

[0062] The oral mucosal delivery system provided in the present application is suitable for the encapsulation of glucose and can stably adhere to the oral mucosa, especially the sublingual region. At the same time, the raw materials are safe and meet the standards for use by neonates, and can achieve the purpose of increasing the blood glucose concentration of neonates.

[0063] For experimental parameters not specified in the following specific embodiments, reference is made to the instructions given in the present application document, and reference may also be made to experimental manuals in the art or other experimental methods known in the art, or to experimental conditions recommended by manufacturers.

[0064] The raw materials and reagents involved in the following specific examples can be obtained from commercial sources, or can be prepared by those skilled in the art according to known methods.

[0065] Example 1

[0066] This embodiment is an oral mucosal delivery system, and the preparation steps are as follows:

[0067] A polyvinyl pyrrolidone (PVP, 10 wt%) ethanol solution and a gallic acid (GA, 5 wt%) ethanol solution were prepared at room temperature, and then the two solutions were mixed and stirred at a mass ratio of PVP:GA of 2:1, and a white precipitate appeared in the system;

[0068] The obtained white precipitate is fished out from the solution, squeezed through a polyethylene plate, and naturally air-dried to prepare a PVP / GA film, which can be used for sublingual adhesion.

[0069] Example 2

[0070] This embodiment is an oral mucosal delivery system, and the preparation steps are the same as those in Example 1, with the main difference being that the mass ratio of PVP to GA is 3:1.

[0071] The specific steps are as follows:

[0072] A polyvinyl pyrrolidone (PVP, 10 wt%) ethanol solution and a gallic acid (GA, 5 wt%) ethanol solution were prepared at room temperature, and then the two solutions were mixed and stirred at a mass ratio of PVP:GA of 3:1, and a white precipitate appeared in the system;

[0073] The obtained white precipitate is fished out from the solution, squeezed through a polyethylene plate, and naturally air-dried to prepare a PVP / GA film, which can be used for sublingual adhesion.

[0074] Example 3

[0075] This embodiment is an oral mucosal delivery system, and the preparation steps are the same as those in Example 1, with the main difference being that the mass ratio of PVP to GA is 1.5:1.

[0076] The specific steps are as follows:

[0077] A polyvinyl pyrrolidone (PVP, 10 wt%) ethanol solution and a gallic acid (GA, 5 wt%) ethanol solution were prepared at room temperature, and then the two solutions were mixed and stirred at a mass ratio of PVP:GA of 1.5:1, and a white precipitate appeared in the system;

[0078] The obtained white precipitate is fished out from the solution, squeezed through a polyethylene plate, and naturally air-dried to prepare a PVP / GA film, which can be used for sublingual adhesion.

[0079] Example 4

[0080] This embodiment is an oral mucosal delivery system, and the preparation steps are the same as those in Example 1, with the main difference being that the mass ratio of PVP to GA is 1:1.

[0081] The specific steps are as follows:

[0082] A polyvinyl pyrrolidone (PVP, 10 wt%) ethanol solution and a gallic acid (GA, 5 wt%) ethanol solution were prepared at room temperature, and then the two solutions were mixed and stirred at a mass ratio of PVP:GA of 1:1, and a white precipitate appeared in the system;

[0083] The obtained white precipitate is fished out from the solution, squeezed through a polyethylene plate, and naturally air-dried to prepare a PVP / GA film, which can be used for sublingual adhesion.

[0084] Comparative Example 1

[0085] This comparative example is an oral mucosal delivery system, and the preparation steps are the same as those of Example 1, with the main difference being that the mass ratio of PVP to GA is 4:1.

[0086] The specific steps are as follows:

[0087] A polyvinyl pyrrolidone (PVP, 10 wt%) ethanol solution and a gallic acid (GA, 5 wt%) ethanol solution were prepared at room temperature, and then the two solutions were mixed and stirred at a mass ratio of PVP:GA of 4:1, and a white precipitate appeared in the system;

[0088] The obtained white precipitate is fished out from the solution, squeezed through a polyethylene plate, and naturally air-dried to prepare a PVP / GA film, which can be used for sublingual adhesion.

[0089] Test example:

[0090] (1) Structural characterization

[0091] The PVP / GA film of Example 1 was tested by Fourier-transform infrared spectroscopy (FTIR): PVP, GA and the PVP / GA film of Example 1 were tested by Fourier-transform infrared spectroscopy, respectively.

[0092] The results are as follows Figure 1 shown. Figure 1 The C=O peak of PVP (1669 cm -1 ) and CN peak (1284cm -1 ) in PVP / GA water film were shifted up to 1623 cm -1 and 1322cm -1 , suggesting the formation of hydrogen bonds between PVP and GA in the PVP / GA film.

[0093] (2) Adhesion performance test

[0094] Cut the pig tongue into a cuboid of about 1.2cm*1.2cm*3cm, and cut the sample to be tested into a square of about 1cm*1cm. Use the sample to be tested to stick the two pieces of pig tongue together for about 5min to 10min. After ensuring that the bonding is successful, use the lap shear standard to test the adhesion of the PVP / GA film at a speed of 20mm / min. The results are as follows Figure 2 As shown. Compared with the mass ratio of PVP to GA being 4:1 (Comparative Example 1), when the mass ratio of PVP to GA is controlled to be (1-3):1 (Examples 1-4), the PVP / GA film has significantly excellent adhesion to the tongue mucosa, and when the mass ratio of PVP to GA is 2:1 (Example 1), the measured adhesion of the PVP / GA film can reach more than 100 kPa. In addition, Figure 3 As shown, the PVP / GA film of Example 1 was rinsed with water, and it can be seen that the PVP / GA film can still firmly adhere to the tongue mucosa under water rinsing.

[0095] (3) Adhesion reversibility test

[0096] The PVP / GA film of Example 1 was adhered to the tongue mucosa and then placed in a 0.5% sodium bicarbonate (NaHCO3) aqueous solution. The adhesion of the PVP / GA film was tested using a tensile tester. The changes in adhesion after different immersion times were measured. The results are as follows: Figure 4-5 As shown, it can be seen that as the immersion time increases, the adhesion gradually decreases and can be easily removed.

[0097] (4) Glucose release test

[0098] Glucose loading:

[0099] Sampling was performed according to a mass ratio of PVP, GA and glucose of 2:1:2, and an ethanol solution of polyvinyl pyrrolidone (PVP, 10wt%) and an ethanol solution of gallic acid (GA, 5wt%) were prepared at room temperature, glucose powder was dispersed in the ethanol solution of polyvinyl pyrrolidone to prepare a suspension, and then the suspension was mixed and stirred with the ethanol solution of gallic acid, and a white precipitate appeared in the system;

[0100] The obtained white precipitate was fished out from the solution, squeezed through a polyethylene plate, and naturally air-dried to prepare a glucose-encapsulated PVP / GA film (the mass percentage of glucose was 40%).

[0101] In vitro glucose release experiment: PVP / GA film loaded with glucose and commercial glucose gel Glutose15 TMPlace it in artificial saliva at 37°C, draw 20 μL of artificial saliva at the set time point, use the glucose detection kit to measure the glucose content in the artificial saliva at different time points, and make an in vitro glucose release curve, such as Figure 6 The results show that the release rate of glucose from PVP / GA film can reach more than 95% in 120 minutes, while the commercial glucose gel Glutose 15 TM The release amount reaches more than 95% in 75 minutes.

[0102] Comparison of in vivo blood sugar-raising effects: The experimental rabbits were divided into a control group, a PVP / GA (glucose) group, and a Glutose 15 TM The experimental rabbits were anesthetized and weighed. PVP / GA film loaded with glucose and commercial glucose gel Glutose 15 were placed under the tongue of the rabbits according to the different groups. TM Each rabbit received about 100 mg / kg of glucose, and the control group did not place anything under the tongue. At the set time point, blood was collected from the rabbit's ear vein, and the rabbit's blood sugar was measured using a peripheral blood glucose monitor to produce an in vivo glucose release curve, such as Figure 7 The results show that the PVP / GA film containing glucose and the commercial glucose gel Glutose 15 TM Both can effectively increase blood sugar, and the PVP / GA film encapsulating glucose still has the ability to increase blood sugar after 60 minutes.

[0103] Sublingual permeability of FITC-glucose: The experimental rabbits were divided into PVP / GA group and Glutose 15 TM The experimental rabbits were anesthetized. PVP / GA film and commercial gel containing FITC-labeled glucose were placed under the tongue of the rabbits according to the different groups. At the set time point, the rabbits were killed, the tongues were taken, frozen sections were made, and the penetration of FITC-glucose was observed using a fluorescence microscope. Figure 8 The results showed that compared with the commercial glucose gel Glutose 15 TM , the glucose-loaded PVP / GA film had significantly better sublingual permeability.

[0104] (5) Biocompatibility assessment

[0105] Cytotoxicity test: HOK cells were added to a 12-well plate (25,000 cells / well) and incubated in a 37°C incubator for 12 hours. The PVP / GA film of Example 1 was then added to the wells containing cells, and the group with normal culture medium was used as a positive control. After incubation for 24 hours, cell viability was assessed using live / dead cell staining. The results are shown in Figure 2. Fig. 9As shown, the cell survival rates of all groups were greater than 98%. This result shows that the PVP / GA film has no cytotoxicity and has good cell biocompatibility.

[0106] In vivo biocompatibility experiment: Newborn mice were divided into a normal control group and a PVP / GA membrane group. After anesthesia, PVP / GA membranes were placed under the tongues of the newborn mice in the PVP / GA membrane group. The newborn mice were killed 2 hours later. The hearts, livers, spleens, lungs, and kidneys of the newborn mice were embedded, fixed, and sliced ​​for HE staining. The results are shown in the figure. Fig.10 As shown, no abnormal changes were found in the important organs of newborn mice (such as heart, liver, spleen, lung, and kidney). This result shows that PVP / GA membrane has high biosafety and biocompatibility, proving that it has great potential in future clinical applications.

[0107] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0108] The above-described embodiments only express several implementation methods of the present application, which is convenient for understanding the technical solution of the present application in detail, but it cannot be understood as limiting the scope of protection of the patent application. It should be pointed out that for ordinary technicians in this field, without departing from the concept of the present application, several modifications and improvements can be made, which all belong to the scope of protection of the present application. It should be understood that the technical solutions obtained by those skilled in the art through logical analysis, reasoning or limited experiments on the basis of the technical solutions provided in the present application are all within the scope of protection of the claims attached to the present application. Therefore, the scope of protection of the patent of this application shall be based on the content of the attached claims, and the description can be used to interpret the content of the claims.

Claims

1. An oral mucosal delivery system, characterized in that The invention comprises a polymer skeleton, wherein the polymer skeleton is formed by polyvinyl pyrrolidone and gallic acid, and the mass ratio of the polyvinyl pyrrolidone to the gallic acid is 2:1; The preparation method of the oral mucosal delivery system comprises the following steps: The polyvinyl pyrrolidone and the gallic acid are respectively prepared into a first solution and a second solution; the solvent in the first solution and the second solution is ethanol; In the first solution, the mass percentage of polyvinyl pyrrolidone is 8% to 12%, and in the second solution, the mass percentage of gallic acid is 3% to 7%; The first solution and the second solution are mixed, stirred, and the precipitated precipitate is collected and dried to prepare the oral mucosal delivery system.

2. The oral mucosal delivery system according to claim 1, characterized in that The oral mucosal delivery system has an adhesion force greater than or equal to 40 kPa.

3. The oral mucosal delivery system according to claim 1, characterized in that The oral mucosal delivery system is immersed in an alkaline aqueous solution, and the adhesive force decreases with the immersion time.

4. The method for preparing the oral mucosal delivery system according to any one of claims 1 to 3, characterized in that: The steps include: The polyvinyl pyrrolidone and the gallic acid are respectively prepared into a first solution and a second solution; the solvent in the first solution and the second solution is ethanol; The first solution and the second solution are mixed, stirred, and the precipitated precipitate is collected and dried to prepare the oral mucosal delivery system.

5. The method for preparing the oral mucosal delivery system according to claim 4, characterized in that: In the first solution, the mass percentage of polyvinyl pyrrolidone is 10%.

6. The method for preparing the oral mucosal delivery system according to claim 4 or 5, characterized in that: In the second solution, the mass percentage of gallic acid is 5%.

7. A pharmaceutical preparation, characterized in that The invention comprises the oral mucosal delivery system according to any one of claims 1 to 3 and an active ingredient loaded in the oral mucosal delivery system.

8. The pharmaceutical preparation according to claim 7, characterized in that The effective ingredient is glucose.

9. Use of the oral mucosal delivery system according to any one of claims 1 to 3 or the pharmaceutical preparation according to any one of claims 7 to 8 in the preparation of a drug for treating or preventing neonatal hypoglycemia.

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