Orally disintegrating tablet for dust mite desensitization therapy and preparation method thereof

Abstract

A method for preparing orally disintegrating tablets for house dust mite desensitization treatment involves taking house dust mite extract, placing it in a supercritical carbon dioxide extractor, adding a mixed solution of sodium bicarbonate and sodium carbonate, and subjecting the extract to supercritical treatment. After treatment, the pH of the resulting solution is adjusted, and then filtered. The filtrate is concentrated under reduced pressure. The concentrate, glycerol, mannitol, sodium chloride, poloxamer 188, and purified water are mixed, filtered again, and the resulting filtrate is ultrasonically treated before being introduced into a mold for cryopreservation tableting. This invention, by pretreating the house dust mite extract to prepare a concentrated solution, then mixing it with other excipients, ultrasonically treating it, and then cryopreserving it, effectively solves the problems of tablet splashing and poor tablet formation during tablet preparation, as well as the problems of poor stability and unsatisfactory disintegration performance of the prepared orally disintegrating tablets. This results in orally disintegrating tablets with a smooth surface, uniform color, and complete disintegration within 10 seconds.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparation technology, specifically to an orally disintegrating tablet for the desensitization treatment of house dust mites and its preparation method. Background Technology

[0002] There are approximately 160 million people worldwide suffering from bronchial asthma, with prevalence rates ranging from 1% to 13% in different countries. In my country, the prevalence is 1% to 4%. It is generally believed that the incidence is higher in children than in adults. Allergic asthma accounts for 80% of infant and young child asthma cases, and the occurrence, development, and persistence of symptoms in most cases of allergic asthma are closely related to house dust mite allergy. 80% of asthma patients test positive for house dust mite prick tests. Epidemiological surveys worldwide have shown that house dust mites are the most significant allergen, and the occurrence, development, acute exacerbations, and persistence of symptoms in most cases of allergic asthma are closely related to house dust mite allergy.

[0003] The World Health Organization (WHO) and the International Federation of Immunological Societies have jointly held three international working conferences on house dust mite allergy, drafting guidance documents on house dust mites and allergic diseases. The WHO's guidance document on immune desensitization clearly states that "desensitization is the only fundamental treatment that can completely cure allergic diseases." Sublingual desensitization therapy is currently only for patients allergic to house dust mites and dust mites. This method is relatively safe and has good patient compliance.

[0004] The mechanism of sublingual desensitization therapy is that the sublingual mucosa contains numerous Langerhans cells. These cells absorb trace amounts of house dust mite allergens, process them into mite polypeptide information, and present this information to Th0 cells, causing them to transform into Th1 cells and preventing allergic reactions. For allergic rhinitis, allergic asthma, allergic conjunctivitis, allergic rashes, allergic urticaria, and other allergic conjunctivitis caused by house dust mites, patients show changes in their immunological indicators before and after sublingual house dust mite immunotherapy. Because the sublingual mucosa is thin, these Langerhans cells on the mucosal surface can capture the signal of the allergen's presence upon contact with the antigen. The allergen vaccine is rapidly absorbed, thus initiating a desensitization reaction. This includes an increase in serum IgG4 levels and an improvement in the Th2 / Th1 cell ratio. Since the medication is administered sublingually, serious adverse reactions such as anaphylactic shock are usually not caused. A very small number of patients may experience mild rashes or mild diarrhea, which resolves upon discontinuation of treatment or dose reduction. Therefore, preparing anti-allergy desensitizing drugs into orally disintegrating tablets is a way to facilitate drug utilization. Summary of the Invention

[0005] The purpose of this invention is to provide an orally disintegrating tablet for the desensitization treatment of house dust mites.

[0006] Another object of the present invention is to provide a method for preparing the above-mentioned orally disintegrating tablets for the treatment of house dust mite desensitization.

[0007] The objective of this invention is achieved through the following technical solution: An orally disintegrating tablet for desensitization treatment of house dust mites is characterized by: pretreatment of house dust mite extract, filtration to collect the filtrate, concentration under reduced pressure to obtain a concentrated solution, mixing it with poloxamer 188, sodium chloride, mannitol and glycerin to form a mixed solution, filtration, ultrasonic treatment, and finally freeze-drying at elevated temperature to produce an orally disintegrating tablet.

[0008] Furthermore, the pretreatment involves placing the dust mite extract in a supercritical carbon dioxide extractor, adding a mixed solution of sodium bicarbonate and sodium carbonate, setting the CO2 flow rate to 6-8 kg / h, the pressure to 10-15 MPa, and the temperature to 25-30°C and maintaining this temperature, for a treatment time of 1-2 hours. After treatment, the treated liquid is collected, the pH of the treated liquid is adjusted, and then filtered.

[0009] Furthermore, the mass ratio of the extract to the mixed solution is 100:40~60, the mass fraction of potassium bicarbonate is 5%~8%, the mass fraction of potassium carbonate is 5%~8%, and the mass ratio of potassium bicarbonate to potassium carbonate is 5:2~3.

[0010] Furthermore, the pH of the treatment solution is adjusted by adding 0.1 mol / L hydrochloric acid to the treatment solution to adjust the pH to 5.0~5.5, and then letting it stand for 12~18 h.

[0011] Furthermore, the vacuum concentration temperature is 40~45℃, the vacuum degree is -0.05~-0.07MPa, and the relative density is 1.02~1.05 when concentrated to 30℃.

[0012] Furthermore, according to the weight parts, the mixture consists of solution 1 and solution 2, wherein solution 1 consists of 20-25 parts of concentrated solution, 6-8 parts of glycerol, 80-120 parts of mannitol microporous solution, 8-12 parts of sodium chloride, and 60-80 parts of purified water, and solution 2 is obtained by dissolving poloxamer 188 in 40-50 parts of purified water.

[0013] Further, in step S2, the purified water in solution 2 is 40-50 parts, heated to 50-55°C, and 0.3-0.5 parts of poloxamer 188 are added at 20-30 rpm to obtain solution 2.

[0014] Furthermore, the ultrasonic treatment involves placing the filtrate prepared in step S2 into an ultrasonic instrument, setting the ultrasonic frequency to 20~30KHz, and the treatment time to 10~15min.

[0015] Furthermore, the cryogenic preparation involves cooling the material to -40 to -45°C at a rate of 10 to 15°C / min, holding it for 1 to 2 hours, and then evacuating it to -0.05 to -0.08 MPa. The temperature is then increased to -5 to -10°C at a rate of 10 to 12°C / min and held for 10 to 12 hours. The temperature is then gradually increased to 5 to 8°C over a period of 30 to 50 minutes and held for 1 to 2 hours. Finally, the temperature is increased to 20 to 25°C at a rate of 2 to 3°C / min and held for 1 to 2 hours. After demolding, the disintegrating tablet is obtained.

[0016] A method for preparing orally disintegrating tablets for house dust mite desensitization treatment, characterized by comprising the following steps: S1. Pre-treatment of dust mite extract: Specifically, dust mite extract is placed in a supercritical carbon dioxide extractor, a mixed solution of sodium bicarbonate and sodium carbonate is added, and after supercritical treatment, the pH of the treated solution is adjusted, then filtered, and the filtrate is concentrated under reduced pressure to obtain a concentrated solution. S2. Mix the concentrate, glycerol, mannitol and sodium chloride, and add purified water to prepare solution 1; separately add purified water to poloxamer 188 to prepare solution 2; add solution 1 to solution 2, mix to obtain a transparent solution, and filter to obtain the filtrate; S3. Sonicate the filtrate; S4. The filtrate after ultrasonic treatment is introduced into a mold for cryopreservation and tableting. After demolding, the orally disintegrating tablet is obtained.

[0017] Furthermore, in step S1, the supercritical treatment involves placing the dust mite extract in a supercritical carbon dioxide extractor, adding a mixed solution of sodium bicarbonate and sodium carbonate, setting the CO2 flow rate to 6-8 kg / h, the pressure to 10-15 MPa, and the temperature to 25-30°C and maintaining it, for a treatment time of 1-2 hours, and collecting the treated liquid after the treatment is completed.

[0018] Furthermore, the mass ratio of the extract to the mixed solution is 100:40~60, the mass fraction of potassium bicarbonate is 5%~8%, the mass fraction of potassium carbonate is 5%~8%, and the mass ratio of potassium bicarbonate to potassium carbonate is 5:2~3.

[0019] Furthermore, in step S1, adjusting the pH of the treatment solution involves adding 0.1 mol / L hydrochloric acid to the treatment solution to adjust the pH to 5.0~5.5, and then letting it stand for 12~18 hours.

[0020] Furthermore, the vacuum concentration temperature is 40~45℃, the vacuum degree is -0.05~-0.07MPa, and the relative density is 1.02~1.05 when concentrated to 30℃.

[0021] Furthermore, according to the weight parts, in step S2 solution 1, the concentrate is 20-25 parts, glycerol is 6-8 parts, mannitol microporous solution is 80-120 parts, sodium chloride is 8-12 parts, and purified water is 60-80 parts.

[0022] Further, in step S2, the purified water in solution 2 is 40-50 parts, heated to 50-55°C, and 0.3-0.5 parts of poloxamer 188 are added at 20-30 rpm to obtain solution 2.

[0023] Furthermore, the ultrasonic treatment involves placing the filtrate prepared in step S2 into an ultrasonic instrument, setting the ultrasonic frequency to 20~30KHz, and the treatment time to 10~15min.

[0024] Furthermore, the cryogenic preparation involves cooling the material to -40 to -45°C at a rate of 10 to 15°C / min, holding it for 1 to 2 hours, and then evacuating it to -0.05 to -0.08 MPa. The temperature is then increased to -5 to -10°C at a rate of 10 to 12°C / min and held for 10 to 12 hours. The temperature is then gradually increased to 5 to 8°C over a period of 30 to 50 minutes and held for 1 to 2 hours. Finally, the temperature is increased to 20 to 25°C at a rate of 2 to 3°C / min and held for 1 to 2 hours. After demolding, the disintegrating tablet is obtained.

[0025] During the cryopreservation process, the disintegrating tablets exhibited obvious problems such as splattering, tablet misshapenness, and cracking.

[0026] The prepared orally disintegrating tablets had unsatisfactory disintegration properties, making it difficult to achieve rapid disintegration within 10 seconds. Furthermore, the tablets exhibited poor stability in terms of appearance during prolonged storage, with spots appearing on the surface and the color darkening and yellowing.

[0027] This invention pretreats dust mite extract to create a concentrated solution, which is then mixed with other excipients, subjected to ultrasonic treatment, and subsequently cryopreserved into tablets. Since the active ingredients in the extract are mainly proteins and enzymes, pretreatment is performed using a supercritical carbon dioxide extractor with a mixture of sodium bicarbonate and sodium carbonate. During this process, the presence of carbon dioxide fluid creates a stable pH buffer system, stabilizing the transfer and stability of the active ingredients. Through this pretreatment step and subsequent ultrasonic treatment, the stability of the active ingredients is improved, while excess gas in the system is removed. This effectively solves problems such as tablet splashing, tablet deformity, and cracking during cryopreservation. It also effectively improves the disintegration performance of orally disintegrating tablets, achieving complete disintegration within 10 seconds.

[0028] A method for preparing orally disintegrating tablets for house dust mite desensitization treatment, characterized by comprising the following steps: S1. Pretreatment of dust mite extract: Specifically, the dust mite extract is placed in a supercritical carbon dioxide extractor, a mixed solution of sodium bicarbonate and sodium carbonate is added, the CO2 flow rate is set to 6-8 kg / h, the pressure to 10-15 MPa, the temperature to 25-30℃ and maintained, and the treatment time is 1-2 h. After treatment, the treated liquid is collected, 0.1 mol / L hydrochloric acid is added to adjust the pH of the solution to 5.0-5.5, and the solution is allowed to stand for 12-18 h. The filtrate is collected by filtration, and the filtrate is concentrated under reduced pressure at a temperature of 40-45℃ and a vacuum degree of -0.05--0.07 MPa until the relative density is 1.02-1.05 (30℃), to obtain a concentrated solution. The mass ratio of the extract to the mixed solution is 100:40-60, the mass fraction of potassium bicarbonate is 5%-8%, the mass fraction of potassium carbonate is 5%-8%, and the mass ratio of potassium bicarbonate to potassium carbonate is 5:2-3. S2. Mix 20-25 parts by weight of concentrated solution, 6-8 parts by weight of glycerol, 80-120 parts by weight of mannitol and 8-12 parts by weight of sodium chloride, add 60-80 parts by weight of purified water, and stir at 20-30 rpm at 20-30°C to obtain solution 1; separately take 40-50 parts by weight of purified water, heat to 50-55°C, and add 0.3-0.5 parts by weight of poloxamer 188 at 20-30 rpm to obtain solution 2; under the same stirring conditions, add solution 1 to solution 2, and continue stirring for 5-8 minutes after the addition is complete to obtain a transparent solution, and filter to obtain the filtrate; S3. The filtrate is subjected to ultrasonic treatment, specifically by placing the filtrate in an ultrasonic instrument, setting the ultrasonic frequency to 20~30KHz, and the treatment time to 10~15min; S4. The filtrate after ultrasound is introduced into a mold for cryogenic preparation. Specifically, the temperature is lowered to -40 to -45°C at a rate of 10 to 15°C / min and held for 1 to 2 hours. After shaping, the vacuum is drawn to -0.05 to -0.08 MPa, and the temperature is raised to -5 to -10°C at a rate of 10 to 12°C / min and held for 10 to 12 hours. Then, the temperature is gradually raised to 5 to 8°C within 30 to 50 minutes and held for 1 to 2 hours. Finally, the temperature is raised to 20 to 25°C at a rate of 2 to 3°C / min and held for 1 to 2 hours. After demolding, the orally disintegrating tablet is obtained.

[0029] The present invention has the following technical effects: In this invention, the dust mite extract is pretreated to form a concentrated solution, which is then mixed with other excipients, subjected to ultrasonic treatment, and then frozen into tablets. This effectively solves the problems of tablet splashing and non-formation during the tablet preparation process, as well as the problems of poor stability and unsatisfactory disintegration performance of the prepared orally disintegrating tablets. As a result, the prepared orally disintegrating tablets have a smooth surface, uniform color, and completely disintegrate within 10 seconds. Detailed Implementation

[0030] The present invention will be specifically described below through embodiments. It should be noted that the following embodiments are only used to further illustrate the present invention and should not be construed as limiting the scope of protection of the present invention. Those skilled in the art can make some non-essential improvements and adjustments to the present invention based on the above description.

[0031] The dust mite extract used in this invention was purchased from Greer Labs dust mite extract, catalog number XPB82D3A2.5, by Beijing Bolede Biotechnology Co., Ltd.

[0032] Example 1 A method for preparing orally disintegrating tablets for house dust mite desensitization treatment includes the following steps: S1. Pretreatment of dust mite extract: Specifically, the dust mite extract is placed in a supercritical carbon dioxide extractor, a mixed solution of sodium bicarbonate and sodium carbonate is added, the CO2 flow rate is set to 7 kg / h, the pressure to 12 MPa, the temperature to 25℃ and maintained, and the treatment time to 2 hours. After treatment, the treated liquid is collected, 0.1 mol / L hydrochloric acid is added to adjust the pH of the solution to 5.5, and the solution is allowed to stand for 15 hours. The filtrate is collected by filtration, and the filtrate is concentrated under reduced pressure at a temperature of 40℃ and a vacuum degree of -0.05 MPa until a concentrated solution with a relative density of 1.02~1.05 at 30℃ is obtained. The mass ratio of the extract to the mixed solution is 100:50, the mass fraction of potassium bicarbonate is 6%, the mass fraction of potassium carbonate is 6%, and the mass ratio of potassium bicarbonate to potassium carbonate is 5:2.5. S2. Mix 22 parts of concentrated solution, 7 parts of glycerol, 100 parts of mannitol and 10 parts of sodium chloride by weight, add 70 parts of purified water, and stir at 25 rpm at 25°C to obtain solution 1; separately take 45 parts of purified water, heat to 50°C, and add 0.4 parts of poloxamer 188 at 25 rpm to obtain solution 2; under the same stirring conditions, add solution 1 to solution 2, and continue stirring for 6 minutes after the addition is complete to obtain a transparent solution, and filter to obtain the filtrate; S3. The filtrate is subjected to ultrasonic treatment, specifically by placing the filtrate in an ultrasonic instrument, setting the ultrasonic frequency to 25KHz, and the treatment time to 12min. S4. The filtrate after ultrasound is introduced into a mold for freeze drying. Specifically, the temperature is lowered to -45°C at a rate of 12°C / min and held for 1 hour. After shaping, the vacuum is drawn to -0.06 MPa, and the temperature is raised to -5°C at a rate of 10°C / min and held for 10 hours. Then, the temperature is gradually raised to 6°C within 40 minutes and held for 1.5 hours. Finally, the temperature is raised to 20°C at a rate of 2°C / min and held for 2 hours. After demolding, the disintegrating tablets are obtained.

[0033] During the cryopreservation process, no tablet splattering occurred, and the final orally disintegrating tablets had a smooth and even surface with a uniform gloss, achieving a tablet formation rate of 98.8%.

[0034] Effectiveness test of the concentrate prepared in Example 1: 1. Guinea pig grouping: 15 guinea pigs were randomly divided into three groups of 5 each. The first group was the experimental group, the second group was the control group 1, and the third group was the blank control group.

[0035] 2. Allergen sensitization: The experimental group of guinea pigs was injected intraperitoneally with the house dust mite extract (before concentration) that had undergone supercritical treatment as described in Example 1, at a dose of 0.5 mg / pig, once a week for a total of 4 times; the control group 1 was injected with the house dust mite extract without supercritical treatment using the same method.

[0036] The control group received an equal volume of physiological saline.

[0037] Allergen testing: In week 5, allergen testing was performed on both groups of guinea pigs.

[0038] (1) ELISA method to detect the level of allergic antibodies in serum: Take guinea pig serum and perform the operation according to the ELISA kit instructions to detect the level of anti-allergen antibodies (IgE) in serum.

[0039] (2) Passive skin allergy test (PCA): Take skin from the back of a guinea pig, prepare intradermal injection points, inject allergen extract and control solution respectively, and observe skin reaction.

[0040] Test results: (1) The results of ELISA showed that the levels of allergen-specific IgE antibodies in the serum of guinea pigs in the experimental group and control group 1 were significantly higher than those in the blank control group, and the changes were basically the same, indicating that the guinea pigs had an allergic reaction to a specific allergen.

[0041] (2) The results of the skin test for allergens showed that the skin on the back of the experimental group and the control group 1 guinea pigs showed obvious redness and swelling allergic reaction, while the blank control group guinea pigs did not show obvious reaction.

[0042] The test results above indicate that after supercritical treatment, the active ingredients in the house dust mite extract did not undergo denaturation or inactivation, and still retain the same effectiveness as the original house dust mite extract, making it suitable for use in subsequent anti-allergy treatments.

[0043] Comparative Example 1 The difference from Example 1 is that, in the case of processing in a CO2 supercritical extraction apparatus, the added processing agent is potassium bicarbonate alone, while the other step parameters are the same as in Example 1.

[0044] During the cryopreservation process, tablet splashing occurred during the -5℃ incubation after shaping. Furthermore, most of the orally disintegrating tablets produced showed varying degrees of cracking, with a tablet formation rate of 70.4%.

[0045] Comparative Example 2 The difference from Example 1 is that, when processing in a CO2 supercritical extraction apparatus, the added processing agent is potassium carbonate alone, while the remaining step parameters are the same as in Example 1.

[0046] During the cryopreservation process, a small number of tablets splashed during the vacuuming process after shaping. In the final orally disintegrating tablets, most tablets showed varying degrees of unevenness on the surface, with a rough and dull surface. The tablet formation rate was 79.6%.

[0047] Comparative Example 3 Unlike Example 1, no ultrasonic treatment was performed before cryo-slide preparation; the remaining steps and parameters were the same as in Example 1.

[0048] During the cryopreservation process, tablets splashed during the vacuuming process after shaping, resulting in most tablets not forming properly, with a tablet formation rate of 25.7%.

[0049] Orally disintegrating tablets with smooth, intact, and uniform color were prepared according to Example 1 and Comparative Examples 1-3 and placed in a temperature of 30℃±2℃ and a humidity of 75%±5%. Samples of 100 tablets were taken at 10, 20, 30, and 40 days to test the properties and disintegration time of each experimental group. The results are shown in Table 1.

[0050] Table 1:

[0051] As shown in the table above, the orally disintegrating tablets prepared by this invention, when naturally placed in an environment with a temperature of 30℃±2℃ and a humidity of 75%±5%, exhibited stable properties over time, with uniform color, no spots, cracks, or other abnormalities. The disintegration time remained within 10 seconds. In contrast, Comparative Examples 1 and 2, which used potassium bicarbonate and potassium carbonate as single treatment agents during supercritical processing, respectively, significantly increased the disintegration time of the orally disintegrating tablets, and the tablets developed cracks and decreased gloss during long-term storage. Comparative Example 3, which did not undergo ultrasonic treatment before freezing, showed obvious spots and uneven coloring in its orally disintegrating tablets during long-term storage.

[0052] In the clinical use of the orally disintegrating tablets for anti-allergy treatment prepared by this invention, it is necessary to redetermine the dosage standard for desensitization therapy. Therefore, the amount of concentrated solution in the orally disintegrating tablets of this invention is unrelated to the dosage used in subsequent treatment.

[0053] Example 2 A method for preparing orally disintegrating tablets for house dust mite desensitization treatment includes the following steps: S1. Pretreatment of dust mite extract: Specifically, the dust mite extract is placed in a supercritical carbon dioxide extractor, a mixed solution of sodium bicarbonate and sodium carbonate is added, the CO2 flow rate is set to 6 kg / h, the pressure to 15 MPa, the temperature to 25℃ and maintained, and the treatment time to 2 hours. After treatment, the treated liquid is collected, 0.1 mol / L hydrochloric acid is added to adjust the pH of the solution to 5.0, and the solution is allowed to stand for 12 hours. The filtrate is collected by filtration, and the filtrate is concentrated under reduced pressure at a temperature of 45℃ and a vacuum degree of -0.05 MPa until a concentrated solution with a relative density of 1.02~1.05 at 30℃ is obtained. The mass ratio of the extract to the mixed solution is 100:40, the mass fraction of potassium bicarbonate is 5%, the mass fraction of potassium carbonate is 5%, and the mass ratio of potassium bicarbonate to potassium carbonate is 5:3. S2. Mix 20 parts of concentrated solution, 6 parts of glycerol, 80 parts of mannitol and 8 parts of sodium chloride by weight, add 60 parts of purified water, and stir at 20 rpm at 30°C to obtain solution 1; separately take 40 parts of purified water, heat to 50°C, and add 0.3 parts of poloxamer 188 at 20 rpm to obtain solution 2; under the same stirring conditions, add solution 1 to solution 2, and continue stirring for 5 min after the addition is complete to obtain a transparent solution, and filter to obtain filtrate; S3. The filtrate is subjected to ultrasonic treatment, specifically by placing the filtrate in an ultrasonic instrument, setting the ultrasonic frequency to 30KHz, and the treatment time to 10min. S4. The filtrate after ultrasound is introduced into a mold for freeze drying. Specifically, the temperature is lowered to -45°C at a rate of 10°C / min and held for 1 hour. After shaping, the vacuum is drawn to -0.05MPa, and the temperature is raised to -8°C at a rate of 12°C / min and held for 12 hours. Then, the temperature is gradually raised to 5°C within 30 minutes and held for 2 hours. Finally, the temperature is raised to 25°C at a rate of 2°C / min and held for 1 hour. After demolding, the disintegrating tablets are obtained.

[0054] In this embodiment, no tablet splattering occurred during the cryopreservation process, and the final orally disintegrating tablets had a smooth, even surface and uniform gloss, with a tablet formation rate of 98.1%. The prepared orally disintegrating tablets had a smooth surface, no spots or cracks, uniform color, and an average disintegration time of 9 seconds. They also exhibited excellent physical properties and disintegration stability during long-term storage.

[0055] Example 3 A method for preparing orally disintegrating tablets for house dust mite desensitization treatment includes the following steps: S1. Pretreatment of dust mite extract: Specifically, the dust mite extract is placed in a supercritical carbon dioxide extractor, a mixed solution of sodium bicarbonate and sodium carbonate is added, the CO2 flow rate is set to 8 kg / h, the pressure to 10 MPa, the temperature to 30℃ and maintained, and the treatment time to 1 hour. After treatment, the treated liquid is collected, 0.1 mol / L hydrochloric acid is added to adjust the pH of the solution to 5.2, and the solution is allowed to stand for 18 hours. The filtrate is collected by filtration, and the filtrate is concentrated under reduced pressure at a temperature of 40℃ and a vacuum degree of -0.07 MPa until a concentrate with a relative density of 1.02~1.05 at 30℃ is obtained. The mass ratio of the extract to the mixed solution is 100:60, the mass fraction of potassium bicarbonate is 8%, the mass fraction of potassium carbonate is 8%, and the mass ratio of potassium bicarbonate to potassium carbonate is 5:2. S2. Mix 25 parts of concentrated solution, 8 parts of glycerol, 120 parts of mannitol and 12 parts of sodium chloride according to the weight ratio, add 80 parts of purified water, and stir at 30 rpm at 30°C to obtain solution 1; separately take 50 parts of purified water, heat to 55°C, and add 0.5 parts of poloxamer 188 at 30 rpm to obtain solution 2; under the same stirring conditions, add solution 1 to solution 2, and continue stirring for 8 minutes after the addition is complete to obtain a transparent solution, and filter to obtain the filtrate; S3. The filtrate is subjected to ultrasonic treatment, specifically by placing the filtrate in an ultrasonic instrument, setting the ultrasonic frequency to 20KHz, and the treatment time to 15min. S4. The filtrate after ultrasonication is introduced into a mold for freeze drying. Specifically, the temperature is lowered to -40℃ at a rate of 15℃ / min and held for 2 hours. After shaping, the vacuum is drawn to -0.08MPa, the temperature is raised to -10℃ at a rate of 12℃ / min and held for 10 hours. Then, the temperature is gradually raised to 8℃ within 50 minutes and held for 1 hour. Finally, the temperature is raised to 20℃ at a rate of 3℃ / min and held for 2 hours. After demolding, the orally disintegrating tablets are obtained.

[0056] In this embodiment, no tablet splattering occurred during the cryopreservation process, and the final orally disintegrating tablets had a smooth, even surface and uniform gloss, with a tablet formation rate of 97.4%. The prepared orally disintegrating tablets had a smooth surface, no spots or cracks, uniform color, and an average disintegration time of 10 seconds. They also exhibited excellent physical properties and disintegration stability during long-term storage.

Claims

1. A method for preparing orally disintegrating tablets for house dust mite desensitization treatment, characterized in that, The steps include the following: S1. Pretreatment of dust mite extract: Specifically, the dust mite extract is placed in a supercritical carbon dioxide extractor, and a mixed solution of potassium bicarbonate and potassium carbonate is added. After supercritical treatment, the pH of the treated solution is adjusted to 5.0-5.5, then filtered. The filtrate is concentrated under reduced pressure until the relative density at 30°C is 1.02-1.05, yielding a concentrated solution. The supercritical treatment involves placing the dust mite extract in a supercritical carbon dioxide extractor, adding a mixed solution of potassium bicarbonate and potassium carbonate, setting the CO2 flow rate to 6-8 kg / h, the pressure to 10-15 MPa, and the temperature to 25-30°C and maintaining it for 1-2 hours. After treatment, the treated solution is collected. The mass ratio of the extract to the mixed solution is 100:40-60, the mass fraction of potassium bicarbonate is 5%-8%, the mass fraction of potassium carbonate is 5%-8%, and the mass ratio of potassium bicarbonate to potassium carbonate is 5:2-3. S2. Mix the concentrate, glycerol, mannitol and sodium chloride, and add purified water to prepare solution 1; separately add purified water to poloxamer 188 to prepare solution 2; add solution 1 to solution 2, mix to obtain a transparent solution, and filter to obtain the filtrate; S3. The filtrate is subjected to ultrasonic treatment, wherein the filtrate prepared in step S2 is placed in an ultrasonic instrument, the ultrasonic frequency is set to 20~30KHz, and the treatment time is 10~15min; S4. The filtrate after ultrasonic treatment is introduced into a mold for cryopreservation and tableting. After demolding, the orally disintegrating tablet is obtained.

2. The method for preparing an orally disintegrating tablet for treating house dust mite allergy as described in claim 1, characterized in that: In step S1, adjusting the pH of the treatment solution involves adding 0.1 mol / L hydrochloric acid to the treatment solution to adjust the pH to 5.0~5.5, and then letting it stand for 12~18 hours.

3. A method for preparing orally disintegrating tablets for house dust mite desensitization therapy as described in claim 1 or 2, characterized in that: The vacuum concentration temperature is 40~45℃, the vacuum degree is -0.05~-0.07MPa, and the relative density is 1.02~1.05 when concentrated to 30℃.

4. The method for preparing an orally disintegrating tablet for house dust mite desensitization treatment as described in claim 3, characterized in that: By weight, the concentrate in solution 1 of step S2 consists of 20-25 parts, glycerol 6-8 parts, mannitol 80-120 parts, sodium chloride 8-12 parts, and purified water 60-80 parts.

5. The method for preparing an orally disintegrating tablet for house dust mite desensitization treatment as described in claim 4, characterized in that: In step S2, 40-50 parts of purified water are added to solution 2. The solution is heated to 50-55°C and 0.3-0.5 parts of poloxamer 188 are added at 20-30 rpm to obtain solution 2.

6. The method for preparing an orally disintegrating tablet for house dust mite desensitization treatment as described in claim 5, characterized in that: The cryogenic preparation involves cooling the material to -40 to -45°C at a rate of 10 to 15°C / min, holding it for 1 to 2 hours, and then evacuating it to -0.05 to -0.08 MPa. The temperature is then increased to -5 to -10°C at a rate of 10 to 12°C / min and held for 10 to 12 hours. The temperature is then gradually increased to 5 to 8°C over a period of 30 to 50 minutes and held for 1 to 2 hours. Finally, the temperature is increased to 20 to 25°C at a rate of 2 to 3°C / min and held for 1 to 2 hours. After demolding, the disintegrating tablets are obtained.

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