Oral preparation of glucose-substituted pyrazole compound as well as preparation method and application of oral preparation

Abstract

The invention discloses an oral preparation of a glucose-substituted pyrazole compound as well as a preparation method and application thereof, and relates to the technical field of medicines, the oral preparation comprises the glucose-substituted pyrazole compound, a cyclodextrin derivative, a filler, a disintegrating agent, a lubricant, a penetration enhancer and a natural absorption-promoting auxiliary material. According to the invention, the glucose-substituted pyrazole compound is clathrated by adopting the phosphorylated derivative of hydroxypropyl-beta-cyclodextrin, so that the solubility and the stability of the medicine are remarkably improved, and the effectiveness and the stability of the medicine in the sublingual tablet are ensured by virtue of a clathration technology, so that the bioavailability of the medicine is improved; when a patient uses the sublingual tablet, the dosage of the medicine can be reduced, side effects possibly caused by the too large dosage of the medicine are reduced, meanwhile, due to the use of the cyclodextrin derivative, the taste of the medicine is improved, stimulation of the medicine to oral mucosa is reduced, the sublingual tablet is more easily accepted by the patient, and the medication experience of the patient is greatly improved.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, in particular to an oral preparation of a glucose-substituted pyrazole compound, a preparation method and an application thereof. Background Art

[0002] In the field of pharmaceutical preparations, glucose-substituted pyrazole compounds have attracted widespread attention from researchers due to their potential medicinal value in the treatment of certain diseases. These compounds have unique mechanisms of action in regulating physiological functions and combating disease pathological processes, and are expected to provide new options for the treatment of various diseases. However, developing these compounds into safe, effective, and highly compliant pharmaceutical preparations faces many challenges, especially sublingual preparations. As a mode of administration that can avoid the first-pass effect of the liver and enable drugs to take effect quickly, they are of great significance for improving drug bioavailability and therapeutic effects. However, the characteristics of glucose-substituted pyrazole compounds themselves, such as low solubility, poor stability, and possible irritation to the oral mucosa, severely limit their application in sublingual tablet preparations.

[0003] In the process of solving the problem of sublingual tablet preparations of glucose-substituted pyrazole compounds, traditional technologies have exposed obvious shortcomings. Although ordinary cyclodextrin can be used to encapsulate drugs to improve their properties, its effect is limited in actual applications. It has a small improvement in the solubility and stability of glucose-substituted pyrazole compounds and cannot fully meet the requirements of sublingual tablet preparations. At the same time, the effect of ordinary cyclodextrin in improving the taste of drugs and reducing irritation to the oral mucosa is also unsatisfactory. In addition, the existing absorption-promoting technology has limitations and lacks an ideal excipient that can effectively promote drug absorption and protect the oral mucosa. Although the existing penetration enhancers can promote the penetration of drugs through the oral mucosa to a certain extent, they often ignore the protection of the oral mucosa. Long-term use may aggravate the irritation to the mucosa and reduce the patient's comfort. These shortcomings make traditional technologies face many difficulties in developing sublingual tablet preparations of glucose-substituted pyrazole compounds and cannot meet the clinical demand for such preparations. Summary of the Invention

[0004] The purpose of the present invention is to make up for the deficiencies of the prior art and provide an oral preparation of a glucose-substituted pyrazole compound, a preparation method and application thereof. The oral preparation can include the glucose-substituted pyrazole compound by using a phosphorylated derivative of hydroxypropyl-β-cyclodextrin. The cyclodextrin derivative has better water solubility and stability, can more effectively include the drug, significantly increase the solubility and stability of the drug, and at the same time improve the taste of the drug and reduce the irritation of the drug to the oral mucosa. The newly added flavonol glycosides extracted from ginkgo leaves and acetylated and modified are used as natural absorption-promoting excipients, which can not only effectively promote the absorption of the drug through the oral mucosa, but also have antioxidant and mucosal protective effects, thereby improving the comprehensive performance of the preparation. In terms of the preparation method, reasonable steps and process parameters are used to ensure that the various components are fully mixed and uniformly, and the prepared sublingual tablets have good disintegration and release properties. The sublingual tablets of the present invention can be quickly absorbed into the blood circulation through sublingual administration, thereby improving the bioavailability of the drug and reducing the dosage and side effects of the drug.

[0005] In order to solve the above technical problems, the present invention provides the following technical solutions: In the first aspect, an oral preparation of a glucose-substituted pyrazole compound comprises a glucose-substituted pyrazole compound, a cyclodextrin derivative, a filler, a disintegrant, a lubricant, a penetration enhancer and a natural absorption-promoting excipient.

[0006] Furthermore, the glucose-substituted pyrazole compound is 1-phenyl-3-methyl-5-OD-glucoside-pyrazole, and the glucose-substituted pyrazole compound is represented by the general formula I:

[0007]

[0008] Furthermore, the cyclodextrin derivative is a phosphorylated derivative of hydroxypropyl-β-cyclodextrin, and the glucose-substituted pyrazole compound and the phosphorylated derivative of hydroxypropyl-β-cyclodextrin are included in a molar ratio of 1:1-1:3 to form an inclusion complex.

[0009] Furthermore, the filler is selected from one or more of mannitol, lactose and microcrystalline cellulose, preferably mannitol, accounting for 40%-70% of the total weight of the tablet.

[0010] Furthermore, the disintegrant is selected from one or more of cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, etc., preferably cross-linked polyvinylpyrrolidone, accounting for 5%-20% of the total weight of the tablet.

[0011] Furthermore, the lubricant is selected from one or more of magnesium stearate, micro powder silica gel, talc, etc., preferably magnesium stearate, accounting for 0.5%-3% of the total weight of the tablet.

[0012] Furthermore, the penetration enhancer is selected from one or more of chitosan, cyclodextrin, oleic acid, etc., preferably chitosan, accounting for 5%-15% of the total weight of the tablet.

[0013] Furthermore, the absorption-promoting auxiliary material of natural origin is flavonol glycosides extracted from ginkgo leaves and modified by acetylation, accounting for 2%-10% of the total weight of the tablet.

[0014] In a second aspect, a method for preparing an oral formulation of a glucose-substituted pyrazole compound comprises the following specific steps:

[0015] Preparation of the inclusion compound: Weigh the prescribed amount of the phosphorylated derivative of hydroxypropyl-β-cyclodextrin and prepare a 5%-20% aqueous solution. Add the glucose-substituted pyrazole compound to the solution, stir at 30°C-50°C for 2h-4h to allow for full inclusion, and freeze-dry to obtain the inclusion compound.

[0016] Mixing: Weigh the flavonol glycosides extracted from Ginkgo biloba leaves and acetylated, place them in a mixing container with the prescribed amount of inclusion compound, filler, disintegrant and permeation enhancer, and mix thoroughly to obtain a mixed powder;

[0017] Granulation: Add an appropriate amount of water or ethanol solution to the mixed powder to form a soft material, granulate through an 18-20 mesh sieve, and dry the granules at 50°C-60°C until the moisture content is less than 5% to obtain dry granules;

[0018] Tablet compression: Add lubricant to the dried granules, mix evenly, adjust the pressure parameters according to the tablet specifications and equipment conditions, and compress them into sublingual tablets.

[0019] In a third aspect, an application of an oral preparation of a glucose-substituted pyrazole compound, wherein the application field of the oral preparation is:

[0020] Main indications: stroke, including cerebral embolism, cerebral hemorrhage, and nerve cell damage;

[0021] Secondary indications: Neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease.

[0022] Compared with the prior art, the oral preparation (sublingual tablet) of a glucose-substituted pyrazole compound and its preparation method and application have the following beneficial effects:

[0023] 1. The present invention uses a phosphorylated derivative of hydroxypropyl-β-cyclodextrin to encapsulate a glucose-substituted pyrazole compound, thereby significantly increasing the solubility and stability of the drug. The inclusion technology ensures the effectiveness and stability of the drug in the sublingual tablet, thereby improving the bioavailability of the drug, allowing patients to reduce the dosage of the drug when using the sublingual tablet and reduce the side effects that may be caused by excessive drug dosage. At the same time, the use of cyclodextrin derivatives also improves the taste of the drug, reduces the irritation of the drug to the oral mucosa, makes the sublingual tablet more easily accepted by patients, and greatly enhances the patient's medication experience.

[0024] 2. The present invention uses flavonol glycosides extracted from ginkgo leaves and acetylated as natural absorption-promoting excipients, which can effectively promote the absorption of drugs through the oral mucosa, and synergize with penetration enhancers to further improve the bioavailability of drugs, so that drugs can enter the blood circulation more quickly and fully to exert therapeutic effects. It also has antioxidant and mucosal protective effects, enriching the functions of the preparation. During sublingual administration, the oral mucosa may be irritated by the drug, and the excipient can protect the mucosa and reduce irritation. At the same time, its antioxidant effect also helps to maintain the stability of the oral environment.

[0025] Other advantages, objects and features of the present invention will be described in part in the following description and, in part, will be apparent to those skilled in the art based on an examination of the following or may be learned from the practice of the invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] To more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. Those skilled in the art can also derive other drawings based on these drawings without inventive effort.

[0027] Figure 1 The present invention is a flow chart of a method for preparing a glucose-substituted pyrazole compound. DETAILED DESCRIPTION

[0028] In order to further illustrate the technical means and effects adopted by the present invention to achieve the predetermined purpose of the invention, the specific implementation methods, structures, features and effects of the present invention are described in detail below in conjunction with the accompanying drawings and preferred embodiments.

[0029] Example 1

[0030] like Figure 1As shown, 20 g of a phosphorylated derivative of hydroxypropyl-β-cyclodextrin was weighed and prepared into a 10% by mass aqueous solution. 10 g of a glucose-substituted pyrazole compound was added to the above solution, and the mixture was stirred at 200 rpm at 40°C for 3 h to allow the two to be fully included. The inclusion solution was then pre-frozen to -30°C for 3 hours, and then freeze-dried at a vacuum degree of 20 Pa and a temperature of -10°C for 12 hours to obtain an inclusion complex.

[0031] 5 g of flavonol glycosides extracted from ginkgo leaves and modified by acetylation were weighed and placed in a three-dimensional mixer with an inclusion compound, 100 g of mannitol, 20 g of cross-linked polyvinylpyrrolidone, and 15 g of chitosan. The mixture was mixed at a speed of 20 rpm for 20 minutes to obtain a mixed powder.

[0032] An appropriate amount of ethanol solution was added to the mixed powder to prepare a soft material, which could be grasped into a ball and would fall apart when lightly pressed. The soft material was sieved through a 20-mesh sieve to prepare granules. The granules were evenly spread in an oven and dried at 55°C to a moisture content of 3% to obtain dry granules.

[0033] The dried granules were added with 2 g of magnesium stearate and mixed in a small three-dimensional mixer at 15 rpm for 5 minutes. The granules were then transferred to the tablet press hopper, and the tablet press parameters such as pressure were adjusted to press the granules into sublingual tablets weighing 150 mg each.

[0034] Using the paddle method and artificial saliva as the release medium, the drug release of the sublingual tablet reached 88% within 10 minutes under the condition of 37℃±0.5℃. Ten healthy rats were selected and fasted for 12 hours, and the sublingual tablet was administered sublingually. The blood of the rats was collected at 0, 15, 30, 45, 60, 90, and 120 minutes after administration to measure the blood drug concentration. The results showed that the blood drug concentration increased rapidly, reaching the peak time at 30 minutes, and the area under the drug-time curve (AUC) was 800ng·h / mL. The relative bioavailability was increased by 60% compared with that of ordinary oral tablets. An in vitro DPPH free radical scavenging experiment was performed, and an appropriate amount of the sublingual tablet extract was taken to prepare solutions of different concentrations. The results showed that when the extract concentration was 0.5mg / mL, the scavenging rate of DPPH free radicals reached 60%.

[0035] Example 2

[0036] Weigh 30g of a phosphorylated derivative of hydroxypropyl-β-cyclodextrin and prepare a 15% aqueous solution. Add 10g of a glucose-substituted pyrazole compound to this solution and stir at 200 rpm at 40°C for 3 hours to allow for complete inclusion complexation. The inclusion complex is then pre-frozen to -30°C for 3 hours and freeze-dried at -10°C under a vacuum of 20 Pa for 12 hours to obtain an inclusion complex.

[0037] 5 g of flavonol glycosides extracted from ginkgo leaves and modified by acetylation were weighed and placed in a three-dimensional mixer with an inclusion compound, 100 g of mannitol, 20 g of cross-linked polyvinylpyrrolidone, and 15 g of chitosan. The mixture was mixed at a speed of 20 rpm for 20 minutes to obtain a mixed powder.

[0038] An appropriate amount of ethanol solution was added to the mixed powder to prepare a soft material, which could be held into a ball and would fall apart when lightly pressed. The soft material was sieved through a 20-mesh sieve to prepare granules. The granules were evenly spread in an oven and dried at 55°C to a moisture content of 3% to obtain dry granules.

[0039] The dried granules were added with 2 g of magnesium stearate and mixed in a small three-dimensional mixer at 15 rpm for 5 minutes. The granules were then transferred to the tablet press hopper, and the tablet press parameters such as pressure were adjusted to press the granules into sublingual tablets weighing 150 mg each.

[0040] Using the paddle method and artificial saliva as the release medium, the drug release of the sublingual tablet reached 92% within 10 minutes at 37℃±0.5℃. Ten healthy rats were selected and fasted for 12 hours, then the sublingual tablet was administered sublingually. Blood was collected from the rats at 0, 15, 30, 45, 60, 90, and 120 minutes after administration to determine the blood drug concentration. The results showed that the blood drug concentration rose rapidly, reaching a peak time of 25 minutes, and the area under the drug-time curve was 900 ng·h / mL. The relative bioavailability was increased by 70% compared with that of ordinary oral tablets. An in vitro DPPH free radical scavenging experiment was performed, and an appropriate amount of the sublingual tablet extract was taken to prepare solutions of different concentrations. The results showed that when the extract concentration was 0.5 mg / mL, the scavenging rate of DPPH free radicals reached 65%.

[0041] Example 3

[0042] 15 g of a phosphorylated derivative of hydroxypropyl-β-cyclodextrin was weighed and prepared into an 8% aqueous solution. 10 g of a glucose-substituted pyrazole compound was added to the above solution and stirred at 200 rpm at 40°C for 3 h to allow the two to be fully included. The inclusion solution was then pre-frozen to -30°C for 3 hours and then freeze-dried at a vacuum degree of 20 Pa and a temperature of -10°C for 12 hours to obtain an inclusion complex.

[0043] 5 g of flavonol glycosides extracted from ginkgo leaves and modified by acetylation were weighed and placed in a three-dimensional mixer with an inclusion compound, 100 g of mannitol, 20 g of cross-linked polyvinylpyrrolidone, and 15 g of chitosan. The mixture was mixed at a speed of 20 rpm for 20 minutes to obtain a mixed powder.

[0044] An appropriate amount of ethanol solution was added to the mixed powder to prepare a soft material, which could be held into a ball and would fall apart when lightly pressed. The soft material was sieved through a 20-mesh sieve to prepare granules. The granules were evenly spread in an oven and dried at 55°C to a moisture content of 3% to obtain dry granules.

[0045] The dried granules were added with 2 g of magnesium stearate and mixed in a small three-dimensional mixer at 15 rpm for 5 minutes. The granules were then transferred to the tablet press hopper, and the tablet press parameters such as pressure were adjusted to press the granules into sublingual tablets weighing 150 mg each.

[0046] Using the paddle method and artificial saliva as the release medium, the drug release amount of the sublingual tablet within 10 minutes was 82% at 37℃±0.5℃. Ten healthy rats were selected and fasted for 12 hours, then the sublingual tablet was administered sublingually. Blood was collected from the rats at 0, 15, 30, 45, 60, 90, and 120 minutes after administration to determine the blood drug concentration. The results showed that the blood drug concentration rose slightly slower, reaching a peak time of 35 minutes, and the area under the drug-time curve (AUC) was 700 ng·h / mL. The relative bioavailability was increased by 50% compared with that of ordinary oral tablets. An in vitro DPPH free radical scavenging experiment was performed, and an appropriate amount of the sublingual tablet extract was taken to prepare solutions of different concentrations. The results showed that when the extract concentration was 0.5 mg / mL, the scavenging rate of DPPH free radicals reached 55%.

[0047]

[0048] In summary, increasing the content of the phosphorylated derivative of hydroxypropyl-β-cyclodextrin makes the in vitro release effect of the sublingual tablet better, the drug release amount is higher, the in vivo pharmacokinetic parameters are better, the peak time is shortened, the AUC is increased, the relative bioavailability is further improved, and the antioxidant performance is also enhanced. However, reducing the content of the derivative is not as good as Example 1 in all aspects of performance, but still has a certain effect.

[0049] Example 4

[0050] Weigh 20 g of a phosphorylated derivative of hydroxypropyl-β-cyclodextrin and prepare a 10% mass fraction aqueous solution. Add 10 g of a glucose-substituted pyrazole compound to the above solution and stir at 200 rpm at 40°C for 3 h to allow the two to be fully included. Then, pre-freeze the inclusion solution to -30°C and maintain it for 3 hours. Then, freeze-dry it at a vacuum degree of 20 Pa and a temperature of -10°C for 12 hours to obtain an inclusion complex.

[0051] 8 g of flavonol glycosides extracted from ginkgo leaves and modified by acetylation were weighed and placed in a three-dimensional mixer with an inclusion compound, 100 g of mannitol, 20 g of cross-linked polyvinylpyrrolidone, and 15 g of chitosan. The mixture was mixed at a speed of 20 rpm for 20 minutes to obtain a mixed powder.

[0052] An appropriate amount of ethanol solution was added to the mixed powder to prepare a soft material, which could be grasped into a ball and would fall apart when lightly pressed. The soft material was sieved through a 20-mesh sieve to prepare granules. The granules were evenly spread in an oven and dried at 55°C to a moisture content of 3% to obtain dry granules.

[0053] The dried granules were added with 2 g of magnesium stearate and mixed in a small three-dimensional mixer at 15 rpm for 5 minutes. The granules were then transferred to the tablet press hopper, and the tablet press parameters such as pressure were adjusted to press the granules into sublingual tablets weighing 150 mg each.

[0054] Using the paddle method and artificial saliva as the release medium, the drug release of the sublingual tablet reached 90% within 10 minutes under the condition of 37℃±0.5℃. Ten healthy rats were selected and fasted for 12 hours, and the sublingual tablet was administered sublingually. The blood of the rats was collected at 0, 15, 30, 45, 60, 90, and 120 minutes after administration to measure the blood drug concentration. The results showed that the blood drug concentration increased rapidly, reaching the peak time at 28 minutes, and the area under the drug-time curve (AUC) was 850ng·h / mL. The relative bioavailability was increased by 65% ​​compared with that of ordinary oral tablets. An in vitro DPPH free radical scavenging experiment was performed, and an appropriate amount of the sublingual tablet extract was taken to prepare solutions of different concentrations. The results showed that when the extract concentration was 0.5mg / mL, the scavenging rate of DPPH free radicals reached 70%.

[0055] Example 5

[0056] Weigh 20 g of a phosphorylated derivative of hydroxypropyl-β-cyclodextrin and prepare a 10% mass fraction aqueous solution. Add 10 g of a glucose-substituted pyrazole compound to the above solution and stir at 200 rpm at 40°C for 3 h to allow the two to be fully included. Then, pre-freeze the inclusion solution to -30°C and maintain it for 3 hours. Then, freeze-dry it at a vacuum degree of 20 Pa and a temperature of -10°C for 12 hours to obtain an inclusion complex.

[0057] 3 g of flavonol glycosides extracted from ginkgo leaves and modified by acetylation were weighed and placed in a three-dimensional mixer with an inclusion compound, 100 g of mannitol, 20 g of cross-linked polyvinylpyrrolidone, and 15 g of chitosan. The mixture was mixed at a speed of 20 rpm for 20 minutes to obtain a mixed powder.

[0058] An appropriate amount of ethanol solution was added to the mixed powder to prepare a soft material, which could be grasped into a ball and would fall apart when lightly pressed. The soft material was sieved through a 20-mesh sieve to prepare granules. The granules were evenly spread in an oven and dried at 55°C to a moisture content of 3% to obtain dry granules.

[0059] The dried granules were added with 2 g of magnesium stearate and mixed in a small three-dimensional mixer at 15 rpm for 5 minutes. The granules were then transferred to the tablet press hopper, and the tablet press parameters such as pressure were adjusted to press the granules into sublingual tablets weighing 150 mg each.

[0060] Using the paddle method and artificial saliva as the release medium, the drug release amount of the sublingual tablet within 10 minutes was 85% at 37℃±0.5℃. Ten healthy rats were selected and fasted for 12 hours, then the sublingual tablet was administered sublingually. Blood was collected from the rats at 0, 15, 30, 45, 60, 90, and 120 minutes after administration to determine the blood drug concentration. The results showed that the blood drug concentration rose slightly slower, reaching a peak time of 32 minutes, and the area under the drug-time curve (AUC) was 750 ng·h / mL. The relative bioavailability was increased by 55% compared with that of ordinary oral tablets. An in vitro DPPH free radical scavenging experiment was performed, and an appropriate amount of the sublingual tablet extract was taken to prepare solutions of different concentrations. The results showed that when the extract concentration was 0.5 mg / mL, the scavenging rate of DPPH free radicals reached 50%.

[0061]

[0062] In summary, by comparing the examples of sublingual tablets with different contents of flavonol glycosides, increasing the content of flavonol glycosides can bring better performance in terms of in vitro release effect, in vivo pharmacokinetics and antioxidant properties, while reducing its content will lead to a decline in performance in all aspects. It can be seen that the content of flavonol glycosides has a significant effect on the in vitro release, in vivo pharmacokinetics and antioxidant properties of sublingual tablets. Reasonable adjustment of its content may optimize the performance of sublingual tablets to meet clinical needs.

[0063] The above description is merely a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Although the present invention has been disclosed as above in terms of a preferred embodiment, it is not intended to limit the present invention. Any person skilled in the art can, without departing from the scope of the technical solution of the present invention, make some changes or modifications to equivalent embodiments using the technical contents disclosed above. However, any brief modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. An oral preparation of a glucose-substituted pyrazole compound, characterized in that: The oral preparation comprises a glucose-substituted pyrazole compound, a cyclodextrin derivative, a filler, a disintegrant, a lubricant, a permeation enhancer and a natural absorption-promoting auxiliary material.

2. The oral preparation of a glucose-substituted pyrazole compound according to claim 1, characterized in that: The glucose-substituted pyrazole compound is 1-phenyl-3-methyl-5-OD-glucoside-pyrazole, and the glucose-substituted pyrazole compound is represented by the general formula I:

3. The oral preparation of a glucose-substituted pyrazole compound according to claim 1, characterized in that: The cyclodextrin derivative is a phosphorylated derivative of hydroxypropyl-β-cyclodextrin. The glucose-substituted pyrazole compound and the phosphorylated derivative of hydroxypropyl-β-cyclodextrin are included in a molar ratio of 1:1-1:3 to form an inclusion compound.

4. The oral preparation of a glucose-substituted pyrazole compound according to claim 1, characterized in that: The filler is selected from one or more of mannitol, lactose and microcrystalline cellulose, preferably mannitol, accounting for 40%-70% of the total weight of the tablet.

5. The oral preparation of a glucose-substituted pyrazole compound according to claim 1, characterized in that: The disintegrant is selected from one or more of cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, etc., preferably cross-linked polyvinylpyrrolidone, accounting for 5%-20% of the total weight of the tablet.

6. The oral preparation of a glucose-substituted pyrazole compound according to claim 1, characterized in that: The lubricant is selected from one or more of magnesium stearate, micro powder silica gel, talc, etc., preferably magnesium stearate, accounting for 0.5% to 3% of the total weight of the tablet.

7. The oral preparation of a glucose-substituted pyrazole compound according to claim 1, characterized in that: The penetration enhancer is selected from one or more of chitosan, cyclodextrin, oleic acid, etc., preferably chitosan, accounting for 5%-15% of the total weight of the tablet.

8. The oral preparation of a glucose-substituted pyrazole compound according to claim 1, characterized in that: The natural absorption-promoting auxiliary material is a flavonol glycoside substance extracted from ginkgo leaves and modified by acetylation, accounting for 2%-10% of the total weight of the tablet.

9. A method for preparing an oral preparation of a glucose-substituted pyrazole compound, the method being used for preparing an oral preparation of a glucose-substituted pyrazole compound according to any one of claims 1 to 8, characterized in that: The method comprises the following specific steps: Preparation of the inclusion compound: Weigh the prescribed amount of the phosphorylated derivative of hydroxypropyl-β-cyclodextrin and prepare a 5%-20% aqueous solution. Add the glucose-substituted pyrazole compound to the solution, stir at 30°C-50°C for 2h-4h to allow for full inclusion, and freeze-dry to obtain the inclusion compound. Mixing: Weigh the flavonol glycosides extracted from Ginkgo biloba leaves and acetylated, place them in a mixing container with the prescribed amount of inclusion compound, filler, disintegrant and permeation enhancer, and mix thoroughly to obtain a mixed powder; Granulation: Add an appropriate amount of water or ethanol solution to the mixed powder to form a soft material, granulate through an 18-20 mesh sieve, and dry the granules at 50°C-60°C until the moisture content is less than 5% to obtain dry granules; Tablet compression: Add lubricant to the dried granules, mix evenly, adjust the pressure parameters according to the tablet specifications and equipment conditions, and compress them into sublingual tablets.

10. Use of an oral preparation of a glucose-substituted pyrazole compound, wherein the oral preparation of a glucose-substituted pyrazole compound according to any one of claims 1 to 8 is characterized in that: The application fields of the oral preparation are: Main indications: stroke, including cerebral embolism, cerebral hemorrhage, and nerve cell damage; Secondary indications: Neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease.

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