Glucose substituted pyrazole compound and borneol composition tablet and preparation method thereof

Abstract

The invention discloses a composition tablet (sublingual tablet) of a glucose-substituted pyrazole compound and borneol as well as a preparation method and application of the composition tablet, and relates to the technical field of medicines. The composition comprises a glucose substituted pyrazole compound, borneol, a mucous membrane penetration enhancer, propylene glycol, a filling agent, a flavoring agent, a sodium citrate-citric acid pH regulator, a disintegrating agent, an adhesive, a lubricant and a porous structure auxiliary agent. Through an elaborately designed composition formula, especially the combination of the glucose-substituted pyrazole compound and the borneol, the bioavailability and absorption efficiency of the medicine during sublingual administration are remarkably improved, the glucose-substituted pyrazole compound serving as an active component has excellent pharmacological activity, and the pharmaceutical composition is suitable for being applied to sublingual administration of sublingual administration of sublingual administration of sublingual administration of sublingual administration of sublingual administration of sublingual administration. The addition of borneol promotes the penetration of the medicine on the mucous membrane, and in addition, the solubility and stability of the medicine are further optimized by adding auxiliary materials such as a mucous membrane penetration enhancer and a pH regulator, so that the effectiveness and safety of the medicine during sublingual administration are ensured.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, in particular to a composition tablet (sublingual tablet) of a glucose-substituted pyrazole compound and borneol, and a preparation method and application thereof. Background Art

[0002] In the field of medical technology, neurological diseases such as stroke, cerebral embolism, nerve cell damage and cerebral hemorrhage have always been the focus of medical attention. The occurrence of these diseases is often accompanied by severe neurological dysfunction and sequelae, which have a great impact on the patient's quality of life and daily life. With the continuous deepening of medical research and the continuous advancement of drug research and development technology, people have begun to explore more efficient, safe and convenient treatment methods. Among them, the treatment of neurological diseases through oral medication has received widespread attention due to its convenience, ease of implementation and good patient compliance.

[0003] However, traditional oral medications often have some shortcomings in the treatment of neurological diseases. On the one hand, due to the particularity and complexity of the nervous system, drugs need to pass through the blood-brain barrier to reach the lesion site, and the molecular structure and physical and chemical properties of traditional drugs often cannot meet this requirement, resulting in many obstacles in the absorption, distribution, metabolism and excretion of drugs in the body. On the other hand, traditional drugs have a long onset time and unstable therapeutic effects, which are difficult to meet clinical urgent needs. In addition, traditional drugs may also cause some side effects and adverse reactions during use, posing potential risks to the patient's health. Therefore, the development of a new, efficient, safe and convenient drug for the treatment of neurological diseases has important clinical significance and social value.

[0004] Therefore, the development of a composition of a glucose-substituted pyrazole compound and borneol (sublingual tablet) and its preparation method and application not only has significant therapeutic effects, but also has lower side effects and adverse reactions, providing a new drug option for the treatment of neurological diseases, and has important clinical significance and social value. Summary of the Invention

[0005] The purpose of the present invention is to make up for the shortcomings of the existing technology and provide a composition tablet (sublingual tablet) of a glucose-substituted pyrazole compound and borneol, as well as its preparation method and application. The composition is specially designed for the treatment of neurological diseases such as stroke and cerebral embolism. By optimizing the ratio and introducing a porous structure, the dissolution rate and bioavailability of the drug are improved.

[0006] To solve the above technical problems, the present invention provides the following technical solutions: On the one hand, a composition of a glucose-substituted pyrazole compound and borneol, wherein the composition is a tablet, preferably a sublingual tablet, comprising a glucose-substituted pyrazole compound, borneol, a mucosal permeation enhancer, propylene glycol, a filler, a flavoring agent, a sodium citrate-citric acid pH regulator, a disintegrant, a binder, a lubricant, and a porous structure aid;

[0007] The glucose-substituted pyrazole compound is 1-phenyl-3-methyl-5-OD-glucoside-pyrazole, the weight portion of the glucose-substituted pyrazole compound is 5-20 parts, and the glucose-substituted pyrazole compound is a compound represented by Formula 1:

[0008]

[0009] The weight portion of the borneol is 0.5-3 parts; the weight portion of the mucosal permeation enhancer is 0.5-5 parts; the weight portion of propylene glycol is 0.1-3 parts; the weight portion of the filler is 20-60 parts; the weight portion of the flavoring agent is 0.1-2 parts; the weight portion of the sodium citrate-citric acid pH regulator is 1-5 parts; the weight portion of the disintegrant is 5-15 parts; the weight portion of the binder is 1-5 parts; the weight portion of the lubricant is 0.5-3 parts; and the weight portion of the porous structure additive is 0.1-3 parts.

[0010] Furthermore, the mucosal penetration enhancer is a fatty acid ester or a bile salt, the fatty acid ester is ethyl laurate, the bile salt is sodium taurocholate, and the weight ratio of the mucosal penetration enhancer to borneol is 1:0.1-6.

[0011] Furthermore, the weight ratio of propylene glycol to borneol is 1:1-3.

[0012] Furthermore, the filler is a single component of microcrystalline cellulose, mannitol or lactose or any combination thereof; when it is a combination, the weight ratio of each component is: microcrystalline cellulose: mannitol is 1:1-3:1; microcrystalline cellulose: lactose is 2:1-5:1; mannitol: lactose is 1:1-2:1.

[0013] Furthermore, the flavoring agent is one of a steviol glycoside derivative and a mogroside compound; the disintegrant is one of low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone or sodium carboxymethyl starch; and the binder is one of hydroxypropyl methylcellulose or povidone K30.

[0014] Furthermore, the lubricant is a single component of magnesium stearate, talc or micro-powder silica gel or any combination thereof; when combined, the weight ratio of each component is: magnesium stearate: talc is 1:2-2:1; magnesium stearate: micro-powder silica gel is 1:3-3:1; talc: micro-powder silica gel is 1:1-3:1.

[0015] Furthermore, the porous structure auxiliary agent is composed of sodium bicarbonate and citric acid, and the molar ratio of the two is 1:1.

[0016] On the other hand, a method for preparing a composition of a glucose-substituted pyrazole compound and borneol is provided, wherein the specific steps of the preparation method are:

[0017] S100, pretreatment of raw materials and excipients: sieve the glucose-substituted pyrazole compound, borneol, mucosal permeation enhancer, filler, flavoring agent, pH adjuster, disintegrant, binder, lubricant and porous structure additive through an 80-100 mesh sieve respectively for later use;

[0018] S200, mixing to prepare a soft material: uniformly mixing a glucose-substituted pyrazole compound, borneol, a mucosal permeation enhancer, a filler, a flavoring agent, a pH adjuster, a disintegrant, and a binder according to a certain proportion, and adding ethanol as a wetting agent to prepare a soft material;

[0019] S300, foaming granulation: adding porous structure additives to the soft material, mixing evenly and then sieving and granulating to form particles containing foaming agent;

[0020] S400, drying and granulating: drying the granules at 40-60°C until the moisture content is ≤2%, and then sieving and granulating the granules;

[0021] S500, tableting: adding a lubricant to the granules after granulation, mixing them evenly, and using a tablet press to compress the granules to prepare a sublingual tablet with a porous structure.

[0022] Furthermore, the composition is used to prepare a drug for treating a disease:

[0023] Main indications: stroke, cerebral embolism, nerve cell damage and cerebral hemorrhage;

[0024] Secondary indications: Amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease

[0025] Compared with the prior art, the composition of the glucose-substituted pyrazole compound and borneol (sublingual tablet), its preparation method and application have the following beneficial effects:

[0026] 1. The present invention significantly improves the bioavailability and absorption efficiency of the drug when administered sublingually through a carefully designed composition formula, especially the combination of a glucose-substituted pyrazole compound and borneol. The glucose-substituted pyrazole compound, as an active ingredient, has excellent pharmacological activity, and the addition of borneol promotes the penetration of the drug on the mucosa. In addition, the present invention further optimizes the solubility and stability of the drug by adding mucosal penetration enhancers and pH regulator excipients, ensuring the effectiveness and safety of the drug when administered sublingually. This new composition formula not only improves the therapeutic effect of the drug, but also reduces the risk and discomfort of medication for patients.

[0027] 2. The present invention forms a micron-sized pore structure inside the tablet through the reaction of sodium bicarbonate and citric acid, which not only improves the dissolution rate of the tablet, but also increases the contact area between the drug and the oral mucosa, thereby further promoting the absorption of the drug. In addition, the presence of the porous structure makes the tablet easier to disintegrate and disperse in the oral cavity, improving the patient's medication compliance and comfort. It not only solves the shortcomings of traditional sublingual tablets in dissolution rate and absorption efficiency, but also provides new ideas and methods for the rapid onset and sustained release of drugs.

[0028] 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

[0029] 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.

[0030] Figure 1 The present invention is a flow chart of a method for preparing a composition of a glucose-substituted pyrazole compound and borneol. DETAILED DESCRIPTION

[0031] 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.

[0032] Example 1:

[0033] Preparation and application of sublingual tablets for the treatment of stroke.

[0034] Prescription composition (based on 1000 tablets):

[0035] Active ingredient:

[0036] Glucose-substituted pyrazole compound (1-phenyl-3-methyl-5-OD-glucoside-pyrazole, compound of formula I): 100 g (weight parts are taken as the middle value 10 parts, calculated as 100 mg per tablet);

[0037] Borneol: 1.5 g (the weight parts are taken as the middle value 1.5 parts, calculated as 1.5 mg per piece);

[0038] Excipients:

[0039] Mucosal penetration enhancer: sodium taurocholate 3g (take 3 parts by weight, with a weight ratio of 2:1 to borneol);

[0040] Propylene glycol: 1.5 g (1:1 weight ratio with borneol);

[0041] Filler: microcrystalline cellulose 300g + mannitol 100g (compound ratio is 3:1, in line with microcrystalline cellulose: mannitol = 1:1-3:1);

[0042] Flavoring agent: 1g of steviol glycoside derivative (1 part by weight);

[0043] pH adjuster: sodium citrate-citric acid 3g (3 parts by weight);

[0044] Disintegrant: low-substituted hydroxypropyl cellulose 10g (10 parts by weight);

[0045] Binder: 3g of hydroxypropyl methylcellulose (3 parts by weight);

[0046] Lubricant: 1.5g magnesium stearate + 4.5g micro powder silica gel (compound ratio is 1:3, in line with magnesium stearate: micro powder silica gel = 1:3-3:1);

[0047] Porous structure additive: sodium bicarbonate 1.2g + citric acid 1.2g (molar ratio 1:1, total weight is 2.4g, meeting the requirement of 0-3 parts).

[0048] Preparation steps, such as Figure 1 As shown:

[0049] Pretreatment of raw materials and excipients: Glucose-substituted pyrazole compounds, borneol, sodium taurocholate, microcrystalline cellulose, mannitol, steviol glycoside derivatives, sodium citrate-citric acid, low-substituted hydroxypropyl cellulose, hydroxypropyl methylcellulose, magnesium stearate, micropowder silica gel, sodium bicarbonate, and citric acid were sieved through 80 meshes respectively to remove agglomerated particles and ensure uniform particle size.

[0050] Mixing to prepare soft material: In a stainless steel mixing container, add glucose-substituted pyrazole compound (100 g), borneol (1.5 g), sodium taurocholate (3 g), microcrystalline cellulose (300 g), mannitol (100 g), steviol glycoside derivative (1 g), sodium citrate-citric acid (3 g), low-substituted hydroxypropyl cellulose (10 g), and hydroxypropyl methylcellulose (3 g) in sequence, turn on the stirrer and mix at low speed (50-80 rpm) for 15 minutes to ensure that the powder is evenly dispersed.

[0051] Slowly add ethanol (about 300 mL) as a wetting agent, stirring while adding, until a uniform, lump-free soft material is formed (it feels moist but not sticky).

[0052] Foaming granulation: Sodium bicarbonate (1.2g) and citric acid (1.2g) are evenly sprinkled on the surface of the soft material, and stirring and mixing are continued for 10 minutes to fully disperse the porous structure additive.

[0053] The granulation is performed using a 16-mesh screen, and the soft material is squeezed through the screen to form particles with a particle size of about 1-2 mm. The particles generate tiny bubbles after contact with sodium bicarbonate and citric acid, forming a preliminary porous structure.

[0054] Drying the granules: Transfer the granules to a hot air circulation drying oven, set the temperature at 50°C, and dry until the moisture content is ≤2% (about 4-6 hours).

[0055] After drying, the granules were sieved with a 20-mesh screen to remove oversized particles or lumps to ensure good granular fluidity.

[0056] Tableting: Add magnesium stearate (1.5 g) and micro-powdered silica gel (4.5 g) to the granules after granulation, and stir at low speed for 5 minutes to mix well.

[0057] Use a rotary tablet press, select a shallow concave die with a diameter of 8 mm, adjust the pressure to a tablet weight of about 500 mg / tablet, and press it into sublingual tablets with a smooth surface and moderate hardness (hardness value 8-12 kg).

[0058] The carbon dioxide gas produced by the reaction of the porous structure additives in the tablets escapes, forming an internal porous structure, which is conducive to rapid absorption by the sublingual mucosa.

[0059] Quality Control:

[0060] Appearance: The tablets are white or off-white, with a smooth surface and no cracks or loose tablets.

[0061] Disintegration time: Take 6 tablets and place them in a sublingual tablet disintegration apparatus at a water temperature of (37±0.5)℃. Complete disintegration should occur within 5 minutes.

[0062] Content uniformity: Randomly select 10 tablets and determine the content of glucose-substituted pyrazole compounds. The content uniformity deviation is ≤±10%.

[0063] Microbial limits: The oral mucosal preparations were tested for microorganisms, with bacterial counts ≤ 100 CFU / g, mold and yeast counts ≤ 10 CFU / g, and no pathogenic Escherichia coli was detected.

[0064] Applicable patients: patients with acute stroke (within 48 hours of onset), especially those with dysphagia or those who need rapid onset of action.

[0065] Dosage and Administration: Take 1 tablet each time, place under the tongue, 2-3 times a day, or as directed by a doctor.

[0066] Mechanism of action:

[0067] Glucose-substituted pyrazole compounds can alleviate neurological deficits after stroke by inhibiting neuronal apoptosis and improving cerebral blood perfusion.

[0068] Borneol synergistically promotes the penetration and absorption of drugs through the sublingual mucosa, and has anti-inflammatory and antioxidant effects, enhancing the neuroprotective effect.

[0069] The porous structure design accelerates tablet disintegration, allowing the drug to be released quickly and contact the abundant blood vessels under the tongue, shortening the onset time (estimated to be effective within 15-30 minutes).

[0070] In summary, this embodiment discloses a glucose-substituted pyrazole compound and borneol sublingual tablet for the treatment of stroke. The prescription contains the main drug, a mucosal permeation enhancer, and a filler excipient. The proportion of each component meets the requirements of the invention. The preparation process involves pretreatment, soft material preparation, foaming granulation, drying and granulation, and tableting to form an internal porous structure to accelerate disintegration and absorption. Quality control covers appearance and disintegration time indicators to ensure compliance with the preparation. It is clinically suitable for patients with acute stroke, has a fast onset of action when taken sublingually, and has both neuroprotective and absorption-promoting effects. Attention should be paid to the dosage and contraindications, and storage conditions also have corresponding requirements.

[0071] Example 2:

[0072] Preparation of sodium taurocholate dosage-adjusted sublingual tablets.

[0073] Prescription adjustment (based on 1000 tablets, only the dosage of sodium taurocholate is changed):

[0074] The dosage of sodium taurocholate (g) was changed to 1.5 parts for the low dosage in scheme A and 4.5 parts for the high dosage in scheme B. The dosages of other ingredients remained unchanged.

[0075] Preparation steps: The same as steps (S100-S500) of Example 1, except that the amount of sodium taurocholate was adjusted, and other excipients and process parameters remained unchanged. The foaming phenomenon during the granulation process and the formation of the porous structure after tableting were observed.

[0076] The produced sublingual tablets were tested, and Table 1 was generated based on the test results.

[0077]

[0078]

[0079] Comparison Table 1

[0080] Mechanism of action of sodium taurocholate: As a mucosal permeation enhancer, it increases the efficiency of drug transmembrane transport by destroying the mucosal lipid bilayer structure, and at the same time acts synergistically with borneol to improve the sublingual absorption rate of the main drug.

[0081] Dosage range advantages:

[0082] Low dosage (1.5 parts): Insufficient penetration-enhancing effect leads to slow drug absorption and the disintegration time is close to the limit, which may affect the clinical onset speed.

[0083] The original dosage (3 parts, the middle value recommended by the invention) achieves the best balance between penetration efficiency, disintegration rate, taste and stability, which not only meets the demand for rapid onset of sublingual tablets, but also avoids the side effects caused by excessive excipients (such as increased bitterness and decreased stability).

[0084] High dosage (4.5 parts): Although it shortens the disintegration time, excessive damage to the mucosal barrier may cause irritation, and the flavoring agent cannot completely mask the bitter taste. At the same time, it increases hygroscopicity and affects the stability of the preparation.

[0085] Technical effect of the invention: By limiting the dosage of sodium taurocholate to 0.5-5 parts and recommending a weight ratio of 1:0.5-3 to borneol, the penetration efficiency and the comprehensive performance of the preparation can be precisely controlled, verifying the scientific nature and practicality of the dosage range of the present invention and ensuring the effectiveness and safety of the sublingual tablet in clinical applications.

[0086] Example 3:

[0087] Preparation of sublingual tablets with adjusted dosage of sodium bicarbonate and citric acid.

[0088] The prescription adjustment (based on 1000 tablets, only the amount of sodium bicarbonate and citric acid was changed, and the molar ratio was fixed at 1:1) is shown in Comparative Table 2.

[0089]

[0090] Table 2

[0091] Preparation steps: The same as steps (S100-S500) of Example 1, only the amount of sodium bicarbonate and citric acid was adjusted, and other excipients and process parameters remained unchanged. The foaming phenomenon during the granulation process and the formation of the porous structure after tableting were observed.

[0092] The produced sublingual tablets were tested, and Table 3 was generated based on the test results.

[0093]

[0094] Comparison Table 3

[0095] Summary: The role of the porous structure additive: Sodium bicarbonate reacts with citric acid (molar ratio 1:1) to generate carbon dioxide, which forms a porous network inside the tablet, accelerating disintegration and drug release. The invention limits its dosage to 0.1-3 parts per million and has the following advantages:

[0096] Trace group (0.1 portion): Insufficient bubbles, compact particles, slow disintegration and release.

[0097] Low-dose group (1.2 parts): A small amount of bubbles were generated, the porous structure was not obvious, and the improvement in disintegration and release efficiency was limited.

[0098] Medium-dose group (2.4 parts, Example 1): The bubbles were uniform, forming an ideal porous structure, and the disintegration time and drug release rate were optimally balanced. It was non-irritating and had good stability.

[0099] High-dose group (3 servings): Although the disintegration time was further shortened, excessive bubble generation led to particle breakage and damaged tablet appearance. In addition, the excessive pores may increase hygroscopicity and cause mild mucosal irritation.

[0100] Technical Effects of the Invention: By limiting the dosage range, the pore size and density of the porous structure can be precisely controlled, ensuring that the sublingual tablet achieves an optimal balance between rapid disintegration (≤5 minutes), efficient drug release (≥80% release in 15 minutes), and safety. This example demonstrates that 2.4 servings (medium dose group) is the ideal dosage, meeting the design objectives of the invention while avoiding the degradation of the formulation quality caused by overdosage.

[0101] Example 4:

[0102] Preparation and comparison of sublingual tablets for storage stability verification:

[0103] Prescription and process:

[0104] The formulation of Example 1 was completely followed, including 100 g of a glucose-substituted pyrazole compound, 1.5 g of borneol, 3 g of sodium taurocholate, 1.5 g of propylene glycol, a filler (a mixture of 300 g of microcrystalline cellulose and 100 g of mannitol), 1 g of a flavoring agent, 1 g of a steviol glycoside derivative, 3 g of a sodium citrate-citric acid pH adjuster, 10 g of a disintegrant, 3 g of a binder, 3 g of hydroxypropyl methylcellulose, a lubricant of 1.5 g of magnesium stearate and 4.5 g of micropowdered silica gel, and 1.2 g of sodium bicarbonate and 1.2 g of citric acid (molar ratio 1:1) as porous structure enhancers. Three batches of sublingual tablets were prepared strictly following the steps of Example 1, with batch numbers 20250423-01, 02, and 03.

[0105] Storage stability comparison experiment design:

[0106] Experimental groups:

[0107] The present invention group: After sealing, place in a cool and dry place with a temperature of ≤25°C and a relative humidity of ≤60%, simulating the storage conditions recommended in the instructions.

[0108] Control group 1: placed in the open air, temperature 25℃, relative humidity 75%, simulating a high humidity and unsealed environment.

[0109] Control group 2: After sealing, the samples were placed in a high temperature environment at 40°C and 75% relative humidity to simulate the accelerated destruction experimental conditions.

[0110] Testing indicators and methods:

[0111] Appearance: Visually inspect the tablets for cracks, discoloration, deliquescence, adhesion, or mold.

[0112] Hardness: Use a hardness tester and the Monsanto method to test, the qualified standard is 8-12kg.

[0113] Disintegration time limit: tested by sublingual tablet disintegration instrument, required to be ≤5 minutes.

[0114] Main drug content: Determined by HPLC (C18 column, detection wavelength 254nm), the content should be 90%-110% of the labeled amount.

[0115] Microbial limit: tested by plate count method and membrane filtration method, the number of bacteria is required to be ≤100 CFU / g, the number of molds and yeasts is required to be ≤10 CFU / g, and no pathogenic bacteria shall be detected.

[0116] The produced sublingual tablets were tested, and comparative Table 4 was generated based on the test results.

[0117]

[0118]

[0119] Comparison Table 4

[0120] Summarize:

[0121] This example verifies the stability advantage of the sublingual tablet of the present invention by simulating different storage conditions:

[0122] Recommended storage conditions (group of the present invention):

[0123] The tablets' appearance, hardness, disintegration time, and active drug content remained stable over a three-month period, and microbial limits met standards. This was attributed to the optimal dosage of the porous structure additive (2.4 parts per million) in the formulation. The resulting uniform microporous structure accelerates disintegration while preventing increased hygroscopicity due to excessive pore size. Furthermore, the sodium citrate-citric acid pH regulator and lubricant system (magnesium stearate + micronized silica gel) enhanced the formulation's resistance to deliquescence.

[0124] High humidity environment (control group 1):

[0125] After one month of open storage, the product showed signs of sticking and excessive disintegration. After three months, mold growth occurred and the active ingredient content decreased by 14.9%. This indicates that sealed packaging is key to maintaining stability, and the recommended storage conditions (sealed packaging + low humidity) can effectively mitigate the risk of moisture absorption by excipients (for example, mannitol is highly hygroscopic, and sealing can block moisture vapor).

[0126] High temperature and high humidity environment (control group 2):

[0127] Despite being sealed, high temperatures accelerated the degradation of the main drug (content decreased by 11.4% over 3 months) and significantly reduced hardness. This suggests that high temperatures should be avoided during clinical storage. However, the present invention, through the synergistic stabilization effect of propylene glycol and borneol (propylene glycol as a solvent reduces the crystal form change of the main drug), still performed better than the control group 1 at high temperatures.

[0128] Technical Effects of the Invention: Through dual optimization of formulation composition and storage conditions, the sublingual tablets of the present invention maintain excellent stability under recommended storage conditions, ensuring safety and efficacy in clinical use. Comparative experiments confirm that deviations from the specified storage conditions (such as open storage and high temperatures) lead to significant degradation of the preparation quality, further highlighting the scientific and practical nature of the present invention's technical solution.

[0129] 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. A composition of a glucose-substituted pyrazole compound and borneol, wherein the composition is a tablet, characterized in that: The composition comprises a glucose-substituted pyrazole compound, borneol, a mucosal permeation enhancer, propylene glycol, a filler, a flavoring agent, a sodium citrate-citric acid pH regulator, a disintegrant, a binder, a lubricant and a porous structure aid; The glucose-substituted pyrazole compound is 1-phenyl-3-methyl-5-O-D-glucoside-pyrazole, the weight portion of the glucose-substituted pyrazole compound is 5-20 parts, and the glucose-substituted pyrazole compound is a compound shown in Formula 1: The weight portion of the borneol is 0.5-3 parts; the weight portion of the mucosal permeation enhancer is 0.5-5 parts; the weight portion of propylene glycol is 0.1-3 parts; the weight portion of the filler is 20-60 parts; the weight portion of the flavoring agent is 0.1-2 parts; the weight portion of the sodium citrate-citric acid pH regulator is 1-5 parts; the weight portion of the disintegrant is 5-15 parts; the weight portion of the binder is 1-5 parts; the weight portion of the lubricant is 0.5-3 parts; and the weight portion of the porous structure additive is 0.1-3 parts.

2. The composition of a glucose-substituted pyrazole compound and borneol according to claim 1, characterized in that: The mucosal permeation enhancer is a fatty acid ester or a bile salt, the fatty acid ester is ethyl laurate, the bile salt is sodium taurocholate, and the weight ratio of the mucosal permeation enhancer to borneol is 1:0.1-6.

3. The composition of a glucose-substituted pyrazole compound and borneol according to claim 1, characterized in that: The weight ratio of the propylene glycol to borneol is 1:1-3.

4. The composition of a glucose-substituted pyrazole compound and borneol according to claim 1, characterized in that: The filler is a single component of microcrystalline cellulose, mannitol or lactose or any combination thereof; when combined, the weight ratio of each component is: microcrystalline cellulose: mannitol is 1:1-3:1; microcrystalline cellulose: lactose is 2:1-5:1; The ratio of mannitol: lactose is 1:1-2:

1.

5. The composition of a glucose-substituted pyrazole compound and borneol according to claim 1, characterized in that: The flavoring agent is one of a stevioside derivative and a mogroside compound; the disintegrant is one of low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone or sodium carboxymethyl starch; and the binder is one of hydroxypropyl methylcellulose or povidone K30.

6. The composition of a glucose-substituted pyrazole compound and borneol according to claim 1, characterized in that: The lubricant is a single component of magnesium stearate, talc or micro-powdered silica gel or any combination thereof; when combined, the weight ratio of each component is: magnesium stearate: talc is 1:2-2:1; The ratio of magnesium stearate: micro powder silica gel is 1:3-3:1; the ratio of talc: micro powder silica gel is 1:1-3:

1.

7. The composition of a glucose-substituted pyrazole compound and borneol according to claim 1, characterized in that: The porous structure auxiliary agent consists of sodium bicarbonate and citric acid, and the molar ratio of the two is 1:

1.

8. The method for preparing a composition of a glucose-substituted pyrazole compound and borneol according to claim 1, wherein the method is used to prepare a composition of a glucose-substituted pyrazole compound and borneol according to any one of claims 1 to 7, characterized in that: The specific steps of the preparation method are: S100, pretreatment of raw materials and excipients: sieve the glucose-substituted pyrazole compound, borneol, mucosal permeation enhancer, filler, flavoring agent, pH adjuster, disintegrant, binder, lubricant and porous structure additive through an 80-100 mesh sieve respectively for later use; S200, mixing to prepare a soft material: uniformly mixing a glucose-substituted pyrazole compound, borneol, a mucosal permeation enhancer, a filler, a flavoring agent, a pH adjuster, a disintegrant, and a binder according to a certain proportion, and adding ethanol as a wetting agent to prepare a soft material; S300, foaming granulation: adding porous structure additives to the soft material, mixing evenly and then sieving and granulating to form particles containing foaming agent; S400, drying and granulating: drying the granules at 40-60°C until the moisture content is ≤2%, and then sieving and granulating the granules; S500, tableting: adding a lubricant to the granules after granulation, mixing them evenly, and using a tablet press to compress the granules to prepare a sublingual tablet with a porous structure.

9. An application of a composition of a glucose-substituted pyrazole compound and borneol, wherein the application is used for a composition prepared from the composition of a glucose-substituted pyrazole compound and borneol according to any one of claims 1 to 7, characterized in that: The composition is used to prepare a treatment for the following diseases: Main indications: stroke, cerebral embolism, nerve cell damage and cerebral hemorrhage; Secondary indications: amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson's disease.

Images