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

Abstract

A preparation method of an orally disintegrating tablet for dust mite desensitization treatment comprises the following steps: placing a dust mite extract in a carbon dioxide supercritical extraction instrument, adding a mixed solution composed of sodium bicarbonate and sodium carbonate, carrying out supercritical treatment, adjusting the pH value of a treated treatment solution, filtering, and carrying out reduced pressure concentration on the filtrate to obtain the orally disintegrating tablet for dust mite desensitization treatment. And mixing the concentrated solution, glycerol, mannitol, sodium chloride, poloxamer 188 and purified water, filtering to obtain filtrate, carrying out ultrasonic treatment, and introducing the filtrate into a mold for freezing and tabletting. According to the preparation method disclosed by the invention, the dust mite extract is pretreated to prepare the concentrated solution, then the concentrated solution is mixed with other auxiliary materials, the mixture is subjected to ultrasonic treatment, and the frozen tablet preparation is carried out, so that the problems that tablets splash and are not formed in the tablet preparation process are effectively solved, and the problems that the prepared orally disintegrating tablets are poor in character stability, non-ideal in disintegration performance and the like are effectively solved; the prepared orally disintegrating tablet is smooth in surface and uniform in color and luster, and the orally disintegrating tablet is completely disintegrated within 10s.

Description

Technical Field

[0001] The invention relates to the technical field of medicine preparation, and in particular to an orally disintegrating tablet for desensitization treatment of dust mites and a preparation method thereof. Background Art

[0002] There are about 160 million bronchial asthma patients in the world, with a prevalence of 1%-13% in different countries, and 1%-4% in my country. It is generally believed that children are more likely to suffer from the disease than adults. Among infants and young children with asthma, allergic asthma accounts for 80%, and the occurrence, development and persistence of symptoms of most allergic asthma are closely related to dust mite allergy. 80% of asthma patients have positive dust mite prick tests. Epidemiological surveys around the world have shown that dust mites are the main allergen, and the occurrence, development, acute onset and persistence of symptoms of most allergic asthma are closely related to dust mite allergy.

[0003] The World Health Organization (WHO) and the International Union of Immunological Societies have jointly held three international dust mite allergy work meetings and drafted guidance documents on dust mites and allergic diseases. The World Health Organization (WHO) clearly pointed out in its guidance document on immune desensitization: "desensitization is the only fundamental treatment method that can completely cure allergic diseases." Sublingual desensitization therapy is currently only for patients who are allergic to dust mites and house dust mites. This method is safe to use and has good patient compliance.

[0004] The mechanism of sublingual desensitization therapy is that there are a lot of Langerhans cells in the sublingual mucosa. After absorbing trace dust mite allergens, they are processed and converted into mite peptide information, which is presented to Th0 cells, so that Th0 cells are transformed into Th1 cells to prevent the occurrence of allergic reactions. For allergic rhinitis, allergic asthma, allergic conjunctivitis, allergic rash, allergic urticaria, allergic conjunctivitis, etc. caused by dust mites, the immunological indicators of patients before and after sublingual dust mite immunotherapy also change. Because the sublingual mucosal tissue is thin, these Langerhans cells located on the surface of the mucosa will capture the signal of the presence of allergens when contacting antigens, and the allergen vaccine can be quickly absorbed, thereby initiating desensitization reactions. Including increased serum IgG4 levels, improved Th2 / Th1 cell ratios, etc. Because it is administered sublingually, serious adverse reactions such as anaphylactic shock usually do not occur. Very few patients occasionally have mild rashes or mild diarrhea, which can be recovered by stopping treatment or reducing the dosage. Therefore, preparing anti-allergic desensitization drugs into orally disintegrating tablets is a way to facilitate drug utilization. Summary of the invention

[0005] The present invention aims to provide an orally disintegrating tablet for desensitization treatment of dust mites.

[0006] Another object of the present invention is to provide a method for preparing the orally disintegrating tablet for desensitization treatment of dust mites.

[0007] The purpose of the present invention is achieved through the following technical solutions: An orally disintegrating tablet for desensitization treatment of dust mites, characterized in that: dust mite extracts are pretreated, the filtrate is filtered and collected, concentrated under reduced pressure to form a concentrated solution, mixed with poloxamer 188, sodium chloride, mannitol and glycerol to form a mixed solution, filtered and then subjected to ultrasonic treatment, and finally heated and freeze-dried to prepare an orally disintegrating tablet.

[0008] Furthermore, the pretreatment is to place the dust mite extract in a supercritical carbon dioxide extraction apparatus, add a mixed solution of sodium bicarbonate and sodium carbonate, set the CO2 flow rate to 6-8 kg / h, the pressure to 10-15 MPa, the temperature to 25-30°C and maintain it, the treatment time is 1-2 hours, and after the treatment is completed, collect the treated liquid, adjust the pH of the treated liquid and filter it.

[0009] Furthermore, the mass ratio of the extract to the mixed solution is 100:40-60, the mass fraction of the potassium bicarbonate is 5%-8%, the mass fraction of the 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 of the solution to 5.0-5.5, and standing for 12-18 hours.

[0011] Furthermore, the temperature of the reduced pressure concentration is 40-45° C., the vacuum degree is -0.05-0.07 MPa, and the relative density is 1.02-1.05 when concentrated to 30° C.

[0012] Furthermore, in terms of weight, the mixed solution consists of solution 1 and solution 2, wherein the concentrate is 20-25 parts, glycerol is 6-8 parts, mannitol micropores are 80-120 parts, sodium chloride is 8-12 parts, and purified water is 60-80 parts to form solution 1, and poloxamer 188 is dissolved in 40-50 parts of purified water to obtain solution 2.

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

[0014] Furthermore, the ultrasonic treatment is to place the filtrate prepared in step S2 in an ultrasonic instrument, set the ultrasonic frequency to 20-30 KHz, and the treatment time to 10-15 min.

[0015] Furthermore, the frozen tableting is performed by cooling the temperature to -40--45°C at a rate of 10-15°C / min, maintaining the temperature for 1-2 hours, evacuating the temperature to -0.05--0.08MPa after shaping, heating the temperature to -5--10°C at a rate of 10-12°C / min, maintaining the temperature for 10-12 hours, then gradually heating the temperature to 5-8°C within 30-50 minutes, maintaining the temperature for 1-2 hours, and then heating the temperature to 20-25°C at a heating rate of 2-3°C / min, maintaining the temperature for 1-2 hours, and obtaining the orally disintegrating tablet after demoulding.

[0016] A method for preparing an orally disintegrating tablet for desensitization treatment of dust mites, characterized in that it comprises the following steps: S1. Pretreatment of the dust mite extract, specifically, placing the dust mite extract in a carbon dioxide supercritical extraction apparatus, adding a mixed solution of sodium bicarbonate and sodium carbonate, and supercritically treating the treated liquid, adjusting the pH of the treated liquid, and then filtering the filtrate, and concentrating the filtrate under reduced pressure to obtain a concentrated solution; S2. The concentrate, glycerol, mannitol and sodium chloride were mixed, and purified water was added to prepare solution 1; purified water was added to prepare solution 2 by adding poloxamer 188; solution 1 was added to solution 2, mixed to obtain a transparent solution, and filtered to obtain a filtrate; S3. subjecting the filtrate to ultrasonic treatment; S4. The filtrate after ultrasonic treatment is introduced into a mold for freezing tableting, and orally disintegrating tablets are obtained after demoulding.

[0017] Furthermore, the supercritical treatment in step S1 is to place the dust mite extract in a carbon dioxide supercritical extraction instrument, add a mixed solution of sodium bicarbonate and sodium carbonate, set the CO2 flow rate to 6-8 kg / h, the pressure to 10-15 MPa, the temperature to 25-30°C and maintain it, the treatment time is 1-2 hours, and after the treatment is completed, the treated liquid is collected.

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

[0019] Furthermore, in step S1, the pH of the treatment solution is adjusted by adding 0.1 mol / L hydrochloric acid to the treatment solution to adjust the pH of the solution to 5.0-5.5, and then standing for 12-18 hours.

[0020] Furthermore, the temperature of the reduced pressure concentration is 40-45° C., the vacuum degree is -0.05-0.07 MPa, and the relative density is 1.02-1.05 when concentrated to 30° C.

[0021] Furthermore, in terms of weight, the solution 1 in step S2 comprises 20 to 25 parts of concentrated solution, 6 to 8 parts of glycerol, 80 to 120 parts of mannitol micropores, 8 to 12 parts of sodium chloride, and 60 to 80 parts of purified water.

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

[0023] Furthermore, the ultrasonic treatment is to place the filtrate prepared in step S2 in an ultrasonic instrument, set the ultrasonic frequency to 20-30 KHz, and the treatment time to 10-15 min.

[0024] Furthermore, the frozen tableting is performed by cooling the temperature to -40--45°C at a rate of 10-15°C / min, maintaining the temperature for 1-2 hours, evacuating the temperature to -0.05--0.08MPa after shaping, heating the temperature to -5--10°C at a rate of 10-12°C / min, maintaining the temperature for 10-12 hours, then gradually heating the temperature to 5-8°C within 30-50 minutes, maintaining the temperature for 1-2 hours, and then heating the temperature to 20-25°C at a heating rate of 2-3°C / min, maintaining the temperature for 1-2 hours, and obtaining the orally disintegrating tablet after demoulding.

[0025] During the freezing tableting process, the orally disintegrating tablets showed obvious problems such as splashing, tablet failure, and cracking.

[0026] The disintegration performance of the prepared orally disintegrating tablets is not ideal, and it is difficult to achieve rapid disintegration within 10 seconds. In addition, during the long-term storage process, the tablet properties of the prepared orally disintegrating tablets are not ideal, spots appear on the surface, and the color becomes darker and yellower.

[0027] In the present invention, dust mite extract is pretreated to prepare a concentrated solution, which is then mixed with other auxiliary materials, ultrasonically treated, and then frozen for tableting. Since the active ingredients in the extract are mainly proteins, enzymes, etc., a carbon dioxide supercritical extractor is used for pretreatment during the pretreatment process, and a mixed solution of sodium bicarbonate and sodium carbonate is added. Under the action of carbon dioxide fluid during the treatment process, a stable pH buffer system is formed, which stabilizes the transfer of the active ingredients in the extract and the stability of the active ingredients in the extract. Through the pretreatment step and subsequent ultrasonic treatment, the stability of the active ingredients is improved, and the excess gas in the system is removed, and the problems of tablet splashing, tablet shapelessness, and cracking during the freezing process are effectively solved. At the same time, the disintegration performance of the orally disintegrating tablet is effectively improved, and complete disintegration can be achieved in 10 seconds.

[0028] A method for preparing an orally disintegrating tablet for desensitization treatment of dust mites, characterized in that it comprises the following steps: S1. Take the dust mite extract for pretreatment, specifically, place the dust mite extract in a carbon dioxide supercritical extractor, add a mixed solution of sodium bicarbonate and sodium carbonate, set the CO2 flow rate to 6-8kg / h, the pressure to 10-15MPa, and the temperature to 25-30°C and maintain it for 1-2h. After the treatment, collect the treated liquid, add 0.1mol / L hydrochloric acid, adjust the pH of the solution to 5.0-5.5, let it stand for 12-18h, filter and collect the filtrate, and reduce the pressure and concentrate the filtrate. Specifically, the concentration temperature is 40-45°C, the vacuum degree is -0.05-0.07MPa, and the filtrate is concentrated to a relative density of 1.02-1.05 (30°C) 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 of the concentrate, 6-8 parts of glycerol, 80-120 parts of mannitol and 8-12 parts of sodium chloride according to weight parts, add 60-80 parts of purified water, stir at 20-30 ℃, and obtain solution 1 at 20-30 rpm; take another 40-50 parts of purified water, heat to 50-55 ℃, add 0.3-0.5 parts of poloxamer 188 at 20-30 rpm to obtain solution 2; add solution 1 to solution 2 under the same stirring conditions, continue stirring for 5-8 minutes after the addition is completed, obtain a transparent solution, and obtain a filtrate after filtering; S3. The filtrate is subjected to ultrasonic treatment, specifically, the filtrate 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 ultrasound is introduced into a mold for frozen tableting, specifically, the temperature is lowered to -40~-45℃ at a rate of 10~15℃ / min, maintained for 1~2h, and evacuated to -0.05~-0.08MPa after shaping, and the temperature is increased to -5~-10℃ at a rate of 10~12℃ / min, and maintained for 10~12h, and then gradually increased to 5~8℃ within 30~50min, and maintained for 1~2h, and then increased to 20-25℃ at a rate of 2~3℃ / min and maintained for 1~2h. After demolding, the orally disintegrating tablets are obtained.

[0029] The present invention has the following technical effects: In the present invention, dust mite extract is pretreated to prepare a concentrated solution, which is then mixed with other auxiliary materials, ultrasonically treated, and then frozen for tableting, thereby effectively solving the problems of tablet splashing and unformed tablets in the tableting process, as well as the problems of poor stability of the prepared orally disintegrating tablets and unsatisfactory disintegration performance, so that the prepared orally disintegrating tablets have a smooth surface and uniform color, and the orally disintegrating tablets are completely disintegrated within 10 seconds. DETAILED DESCRIPTION

[0030] The present invention is described in detail below through examples. It is necessary to point out that the following examples are only used to further illustrate the present invention and cannot be understood 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-mentioned contents of the present invention.

[0031] The dust mite extract used in the present invention was purchased from Greer Labs dust mite extract of Beijing Bolide Biotechnology Co., Ltd., with the product number XPB82D3A2.5.

[0032] Example 1 A method for preparing an orally disintegrating tablet for desensitization treatment of dust mites comprises the following steps: S1. Take the dust mite extract for pretreatment, specifically, place the dust mite extract in a carbon dioxide supercritical extractor, add a mixed solution of sodium bicarbonate and sodium carbonate, set the CO2 flow rate to 7kg / h, the pressure to 12MPa, the temperature to 25°C and maintain, the treatment time is 2h, the treatment is completed, collect the treated liquid, add 0.1mol / L hydrochloric acid, adjust the solution pH to 5.5, let it stand for 15h, filter and collect the filtrate, and reduce the pressure and concentrate the filtrate. The specific concentration temperature is 40°C, the vacuum degree is -0.05MPa, and the relative density of the concentrated solution is 1.02~1.05 when concentrated to 30°C; 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 the concentrate, 7 parts of glycerol, 100 parts of mannitol and 10 parts of sodium chloride according to weight parts, add 70 parts of purified water, stir at 25 rpm at 25 ° C to obtain solution 1; take another 45 parts of purified water, heat to 50 ° C, add 0.4 parts of poloxamer 188 at 25 rpm to obtain solution 2; add solution 1 to solution 2 under the same stirring conditions, continue stirring for 6 minutes after the addition is completed, and obtain a transparent solution, which is filtered to obtain a filtrate; S3. The filtrate is subjected to ultrasonic treatment, specifically, the filtrate is placed in an ultrasonic instrument, the ultrasonic frequency is set to 25KHz, and the treatment time is 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, maintained for 1 hour, evacuated to -0.06MPa after shaping, and the temperature is increased to -5°C at a rate of 10°C / min, maintained for 10 hours, and then gradually increased to 6°C within 40 minutes, maintained for 1.5 hours, and then increased to 20°C at a rate of 2°C / min and maintained for 2 hours. After demolding, the orally disintegrating tablets are obtained.

[0033] During the freezing tableting process, there was no problem of tablet splashing, and the surface of the orally disintegrating tablets finally prepared was flat and smooth, with a uniform gloss, and the tablet forming rate was 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, with 5 in each group. 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 guinea pigs in the experimental group were injected intraperitoneally with the dust mite extract (before concentration) after supercritical treatment in Example 1, with a dose of 0.5 mg / guinea pig, once a week, for a total of 4 injections; the control group 1 was injected with the dust mite extract without supercritical treatment in the same way.

[0036] The control group was injected with an equal volume of saline.

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

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

[0039] (2) Passive cutaneous allergy test (PCA): The skin on the back of the guinea pig is used to prepare intradermal injection points, and allergen extracts and control solutions are injected respectively to observe the skin reaction.

[0040] Test results: (1) The results of ELISA test 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 levels of change were basically the same, indicating that guinea pigs had an allergic reaction to specific allergens.

[0041] (2) The results of the allergen skin test showed that the guinea pigs in the experimental group and the control group 1 had obvious allergic reactions with redness and swelling on their backs, while the guinea pigs in the blank control group did not show obvious reactions.

[0042] The above test results indicate that after supercritical treatment, the active ingredients in the dust mite extracts do not undergo denaturation or inactivation, and still have the same effectiveness as the original dust mite extracts, and can be used in subsequent anti-allergic treatment drugs.

[0043] Comparative Example 1 Compared with Example 1, the difference is that when treating in the CO2 supercritical extraction apparatus, the added treating agent is a single potassium bicarbonate, and the remaining step parameters are the same as those in Example 1.

[0044] During the frozen tableting process, tablet splashing occurred during the -5°C insulation process after shaping, and in the orally disintegrating tablets finally prepared, most tablets were observed to have cracks of varying degrees, and the tablet forming rate was 70.4%.

[0045] Comparative Example 2 Compared with Example 1, the difference is that when treating in the CO2 supercritical extraction apparatus, the added treating agent is a single potassium carbonate, and the remaining step parameters are the same as those in Example 1.

[0046] During the freezing tableting process, a small amount of tablets splashed during the vacuuming process after shaping, and in the orally disintegrating tablets finally prepared, it was observed that the surfaces of most tablets were uneven to varying degrees, rough and matte, and the tablet forming rate was 79.6%.

[0047] Comparative Example 3 The difference from Example 1 is that no ultrasonic treatment is performed before freezing and slicing, and the remaining step parameters are the same as those in Example 1.

[0048] During the freezing tableting process, tablet splashing occurred during the vacuuming process after shaping, resulting in most tablets not being formed, and the tablet forming rate was 25.7%.

[0049] Select Example 1 and Comparative Examples 1-3 to prepare smooth, intact, uniformly colored orally disintegrating tablets and place them in a temperature of 30°C ± 2°C and a humidity of 75% ± 5%. Take 100 tablets at 10 days, 20 days, 30 days, 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 can be seen from the above table, the orally disintegrating tablets prepared by the present invention are naturally placed in an environment with a temperature of 30°C ± 2°C and a humidity of 75% ± 5%. As time goes by, the properties of the orally disintegrating tablets are stable, the color is uniform and unchanged, no spots, cracks, etc. are produced, and the disintegration time is maintained within 10s. In the supercritical treatment process, Comparative Examples 1 and 2 respectively use single potassium bicarbonate and potassium carbonate as treatment agents, which significantly increase the disintegration time of the orally disintegrating tablets, and the tablets have cracks and gloss reduction during long-term placement. Comparative Example 3 was not ultrasonically treated before frozen tableting, and the orally disintegrating tablets had obvious spots and uneven color during long-term placement.

[0052] During clinical use of the orodisintegrating tablet for antiallergic treatment prepared by the present invention, the dosage standard for desensitization treatment needs to be re-determined. Therefore, the dosage of the concentrated solution in the orodisintegrating tablet of the present invention has nothing to do with the dosage used for subsequent treatment.

[0053] Example 2 A method for preparing an orally disintegrating tablet for desensitization treatment of dust mites comprises the following steps: S1. Take the dust mite extract for pretreatment, specifically, place the dust mite extract in a carbon dioxide supercritical extractor, add a mixed solution of sodium bicarbonate and sodium carbonate, set the CO2 flow rate to 6kg / h, the pressure to 15MPa, the temperature to 25°C and maintain, the treatment time is 2h, and after the treatment, collect the treated liquid, add 0.1mol / L hydrochloric acid, adjust the solution pH to 5.0, let it stand for 12h, filter and collect the filtrate, and reduce the pressure and concentrate the filtrate. The specific concentration temperature is 45°C, the vacuum degree is -0.05MPa, and the relative density of the concentrated solution is 1.02~1.05 when concentrated to 30°C; 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 the concentrate, 6 parts of glycerol, 80 parts of mannitol and 8 parts of sodium chloride according to weight parts, add 60 parts of purified water, stir at 20 rpm at 30 ° C to obtain solution 1; take another 40 parts of purified water, heat to 50 ° C, add 0.3 parts of poloxamer 188 at 20 rpm to obtain solution 2; add solution 1 to solution 2 under the same stirring conditions, continue stirring for 5 minutes after the addition is completed, and obtain a transparent solution, which is filtered to obtain a filtrate; S3. The filtrate is subjected to ultrasonic treatment, specifically, the filtrate is placed in an ultrasonic instrument, the ultrasonic frequency is set to 30KHz, and the treatment time is 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, maintained for 1 hour, evacuated to -0.05MPa after shaping, and the temperature is increased to -8°C at a rate of 12°C / min, maintained for 12 hours, and then gradually increased to 5°C within 30 minutes, maintained for 2 hours, and then increased to 25°C at a rate of 2°C / min and maintained for 1 hour. After demolding, the orally disintegrating tablets are obtained.

[0054] In the frozen tableting process of this embodiment, there is no problem of tablet splashing, and the surface of the orally disintegrating tablet finally prepared is flat and smooth, the gloss is uniform, and the tablet forming rate is 98.1%. The surface of the orally disintegrating tablet prepared is smooth, without spots or cracks, the color is uniform, the average disintegration time is 9s, and the physical properties and disintegration time stability are excellent during long-term storage.

[0055] Example 3 A method for preparing an orally disintegrating tablet for desensitization treatment of dust mites comprises the following steps: S1. Take the dust mite extract for pretreatment, specifically, place the dust mite extract in a carbon dioxide supercritical extractor, add a mixed solution of sodium bicarbonate and sodium carbonate, set the CO2 flow rate to 8kg / h, the pressure to 10MPa, the temperature to 30°C and maintain, the treatment time is 1h, the treatment is completed, collect the treated liquid, add 0.1mol / L hydrochloric acid, adjust the solution pH to 5.2, let stand for 18h, filter and collect the filtrate, and reduce the pressure and concentrate the filtrate. The specific concentration temperature is 40°C, the vacuum degree is -0.07MPa, and the relative density of the concentrated solution is 1.02~1.05 at 30°C; 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 the concentrate, 8 parts of glycerol, 120 parts of mannitol and 12 parts of sodium chloride according to weight parts, add 80 parts of purified water, stir at 30 rpm at 30 ° C to obtain solution 1; take another 50 parts of purified water, heat to 55 ° C, add 0.5 parts of poloxamer 188 at 30 rpm to obtain solution 2; add solution 1 to solution 2 under the same stirring conditions, continue stirring for 8 minutes after the addition is completed, and obtain a transparent solution, which is filtered to obtain a filtrate; S3. The filtrate is subjected to ultrasonic treatment, specifically, the filtrate is placed in an ultrasonic instrument, the ultrasonic frequency is set to 20KHz, and the treatment time is 15min; S4. The filtrate after ultrasound is introduced into a mold for freeze drying, specifically, the temperature is lowered to -40°C at a rate of 15°C / min, maintained for 2 hours, evacuated to -0.08MPa after shaping, and the temperature is increased to -10°C at 12°C / min, maintained for 10 hours, and then gradually increased to 8°C within 50 minutes, maintained for 1 hour, and then increased to 20°C at a rate of 3°C / min and maintained for 2 hours. After demolding, the orally disintegrating tablets are obtained.

[0056] In the frozen tableting process of this embodiment, there is no problem of tablet splashing, and the surface of the orally disintegrating tablet finally prepared is flat and smooth, with uniform gloss, and the tablet forming rate is 97.4%. The surface of the orally disintegrating tablet prepared is smooth, without spots or cracks, with uniform color, and the average disintegration time is 10s. The physical properties and disintegration time stability during long-term placement are excellent.

Claims

1. A method for preparing an orally disintegrating tablet for desensitization treatment of dust mites, characterized in that: The steps include: S1. Pretreatment of the dust mite extract, specifically, placing the dust mite extract in a carbon dioxide supercritical extraction apparatus, adding a mixed solution of sodium bicarbonate and sodium carbonate, and supercritically treating the treated liquid, adjusting the pH of the treated liquid, and then filtering the filtrate, and concentrating the filtrate under reduced pressure to obtain a concentrated solution; S2. The concentrate, glycerol, mannitol and sodium chloride were mixed, and purified water was added to prepare solution 1; purified water was added to prepare solution 2 by adding poloxamer 188; solution 1 was added to solution 2, mixed to obtain a transparent solution, and filtered to obtain a filtrate; S3. subjecting the filtrate to ultrasonic treatment; S4. The filtrate after ultrasonic treatment is introduced into a mold for freezing tableting, and orally disintegrating tablets are obtained after demoulding.

2. The method for preparing an orally disintegrating tablet for desensitization treatment of dust mites according to claim 1, characterized in that: The supercritical treatment in step S1 is to place the dust mite extract in a carbon dioxide supercritical extraction instrument, add a mixed solution consisting of sodium bicarbonate and sodium carbonate, set the CO2 flow rate to 6-8kg / h, the pressure to 10-15MPa, the temperature to 25-30°C and maintain it, the treatment time is 1-2h, and the treatment liquid is collected after the treatment is completed.

3. The method for preparing an orally disintegrating tablet for desensitization treatment of dust mites according to claim 1 or 2, characterized in that: 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.

4. A method for preparing an orally disintegrating tablet for treating dust mite allergy according to any one of claims 1 to 3, characterized in that: In step S1, the pH of the treatment solution is adjusted by adding 0.1 mol / L hydrochloric acid to the treatment solution to adjust the pH of the solution to 5.0-5.5, and then standing for 12-18 hours.

5. A method for preparing an orally disintegrating tablet for desensitization treatment of dust mites according to any one of claims 1 to 4, characterized in that: The temperature of the reduced pressure concentration is 40-45° C., the vacuum degree is -0.05-0.07 MPa, and the relative density is 1.02-1.05 when concentrated to 30° C.

6. The method for preparing an orally disintegrating tablet for desensitization treatment of dust mites according to claim 5, characterized in that: In terms of weight, the solution 1 in step S2 comprises 20 to 25 parts of concentrated solution, 6 to 8 parts of glycerol, 80 to 120 parts of mannitol micropores, 8 to 12 parts of sodium chloride, and 60 to 80 parts of purified water.

7. The method for preparing an orally disintegrating tablet for desensitization treatment of dust mites according to claim 6, characterized in that: In step S2, the purified water in solution 2 is 40-50 parts, which 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.

8. A method for preparing an orally disintegrating tablet for treating dust mite allergy according to claim 6 or 7, characterized in that: The ultrasonic treatment is to place the filtrate prepared in step S2 in an ultrasonic instrument, set the ultrasonic frequency to 20-30 KHz, and the treatment time to 10-15 minutes.

9. The method for preparing an orally disintegrating tablet for desensitization treatment of dust mites according to claim 8, characterized in that: The frozen tableting comprises cooling to -40--45°C at a rate of 10-15°C / min, maintaining for 1-2 hours, evacuating to -0.05--0.08MPa after shaping, heating to -5--10°C at a rate of 10-12°C / min, maintaining for 10-12 hours, then gradually heating to 5-8°C within 30-50 minutes, maintaining for 1-2 hours, and then heating to 20-25°C at a heating rate of 2-3°C / min, maintaining for 1-2 hours, and obtaining orally disintegrating tablets after demoulding.

10. A method for preparing an orally disintegrating tablet for desensitization treatment of dust mites, characterized in that: The steps include: S1. Take the dust mite extract for pretreatment, specifically, place the dust mite extract in a carbon dioxide supercritical extractor, add a mixed solution of sodium bicarbonate and sodium carbonate, set the CO2 flow rate to 6-8kg / h, the pressure to 10-15MPa, and the temperature to 25-30°C and maintain it for 1-2h. After the treatment, collect the treated liquid, add 0.1mol / L hydrochloric acid, adjust the pH of the solution to 5.0-5.5, let it stand for 12-18h, filter and collect the filtrate, and reduce the pressure and concentrate the filtrate. Specifically, the concentration temperature is 40-45°C, the vacuum degree is -0.05-0.07MPa, and the filtrate is concentrated to a relative density of 1.02-1.05 (30°C) 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 of the concentrate, 6-8 parts of glycerol, 80-120 parts of mannitol and 8-12 parts of sodium chloride according to weight parts, add 60-80 parts of purified water, stir at 20-30 ℃, and obtain solution 1 at 20-30 rpm; take another 40-50 parts of purified water, heat to 50-55 ℃, add 0.3-0.5 parts of poloxamer 188 at 20-30 rpm to obtain solution 2; add solution 1 to solution 2 under the same stirring conditions, continue stirring for 5-8 minutes after the addition is completed, obtain a transparent solution, and obtain a filtrate after filtering; S3. The filtrate is subjected to ultrasonic treatment, specifically, the filtrate 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 ultrasound is introduced into a mold for frozen tableting, specifically, the temperature is lowered to -40~-45℃ at a rate of 10~15℃ / min, maintained for 1~2h, and evacuated to -0.05~-0.08MPa after shaping, and the temperature is increased to -5~-10℃ at a rate of 10~12℃ / min, and maintained for 10~12h, and then gradually increased to 5~8℃ within 30~50min, and maintained for 1~2h, and then increased to 20-25℃ at a rate of 2~3℃ / min and maintained for 1~2h. After demolding, the orally disintegrating tablets are obtained.

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