A solvent system for the contents of cold soft capsules and cold soft capsules

Abstract

The invention discloses a solvent system for the contents of a cold soft capsule, a cold soft capsule, and a preparation method of the cold soft capsule, and belongs to the technical field of pharmaceutical preparations. The invention provides a solvent system for the contents of a cold soft capsule, which comprises the following components by weight: 20-90 parts of a solvent and 1 to 20 parts of a cosolvent, and a plurality of cold soft capsules of the solvent system. The solvent system of the contents has low cost and good stability, and the cold soft capsules produced by key process steps have high bioavailability, rapid effect, good stability, and low cost.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, and in particular to a solvent system for the contents of cold soft capsules and the cold soft capsules. Background Art

[0002] Cold is a common acute upper respiratory tract viral infection disease, mostly caused by rhinovirus, parainfluenza virus, respiratory syncytial virus, echovirus, coxsackievirus, coronavirus, adenovirus, etc. The incidence rate is particularly high in spring and winter. Clinical manifestations include nasal congestion, sneezing, runny nose, fever, cough, headache, sore throat, etc., which make people feel very uncomfortable and can affect normal life in severe cases.

[0003] There are many kinds of medicines for treating colds. Since the safety of western medicine is relatively transparent and effective, it is very popular. Since there are many symptoms of colds, cold medicines are mostly compound preparations. Compound preparations mainly utilize the synergistic effect between each medicine to give play to the advantages of each medicine and achieve the purpose of symptomatic treatment. For western medicine, the composition of cold medicine mainly includes the following types of medicines: antipyretic analgesics, adrenergic receptor agonists, antihistamines, antitussive expectorants, antiviral drugs, etc. The disadvantage of the current commercially available white and black anti-cold medicine is that the medicine is a tablet, which takes effect slowly and is not easily absorbed by the human body, reducing the bioavailability of the active ingredient. In addition, the cost of the current cold soft capsule is higher than that of tablets. Although it can improve the bioavailability of the active ingredient, it is poor in marketability.

[0004] Therefore, how to provide a solvent system for the contents of cold soft capsules and cold soft capsules with high bioavailability, rapid effect, good stability and low cost and a preparation method thereof are problems that technicians in this field need to solve urgently. Summary of the invention

[0005] In view of this, the object of the present invention is to provide a solvent system for the contents of cold soft capsules and raw cold soft capsules and a preparation method thereof, wherein the solvent system of the contents is low in cost and has good stability, and the cold soft capsules produced through key process steps have high bioavailability, rapid effect, good stability, and low cost.

[0006] In order to achieve the above object, the present invention adopts the following technical solution:

[0007] A solvent system for the contents of cold soft capsules comprises the following components by weight: 20-90 parts of solvent and 1-20 parts of co-solvent.

[0008] Preferably, the solvent is selected from one or more of polyethylene glycol, propylene glycol, glycerol and water. Further, the polyethylene glycol can be selected from one or more of polyethylene glycol 200, polyethylene glycol 400 and polyethylene glycol 600.

[0009] The technical effect of adopting the above technical solution is that the above solvent and the cold medicine can form a clear and transparent solution, which can completely dissolve the cold medicine.

[0010] Preferably, the solvent is a mixture of polyethylene glycol, propylene glycol and water. Further, the polyethylene glycol can be selected from one or more of polyethylene glycol 200, polyethylene glycol 400 and polyethylene glycol 600.

[0011] The technical effect of adopting the above technical scheme is that the composition of polyethylene glycol, propylene glycol or glycerin and water can increase the solubility of cold medicines, especially acetaminophen medicines.

[0012] Preferably, the cosolvent is povidone. Further, the povidone is selected from one or more of povidone 12, povidone 17, povidone 25, povidone 29-32, and povidone 30.

[0013] The technical effect of adopting the above technical solution is that povidone plays a role of solubility aid and can inhibit the recrystallization and precipitation of active ingredients. The peroxide contained in the co-solvent povidone will affect the chemical stability of the product, and the cost of povidone is high. Under the premise of ensuring good product quality, the mass percentage of povidone is controlled at a lower level, thereby reducing costs.

[0014] A cold soft capsule, comprising the above-mentioned solvent system, wherein the active ingredients in the cold soft capsule are selected from one or more of acetaminophen, dextromethorphan hydrobromide, doxylamine succinate, phenylephrine hydrochloride, pseudoephedrine hydrochloride, guaifenesin glyceryl ether, diphenhydramine hydrochloride and chlorpheniramine maleate.

[0015] The technical effect of adopting the above technical scheme is: through a specific solvent system, it can be applied to multiple active ingredients of cold medicines, all of which have the advantages of high bioavailability, rapid effect, good stability, etc.

[0016] Preferably, the following components are included by weight: 10-35 parts of the active ingredient, 20-90 parts of the solvent, and 1-20 parts of the co-solvent.

[0017] Preferably, the active ingredients are acetaminophen, dextromethorphan hydrobromide and doxylamine succinate, and the weight ratio is (25-29): (1.0-1.5): (0.4-0.6).

[0018] Preferably, the following components are included by weight percentage: 25-29 parts of acetaminophen, 1.0-1.5 parts of dextromethorphan hydrobromide, 0.4-0.6 parts of doxylamine succinate, 2-3 parts of povidone, 2.5-10 parts of purified water, 45-65 parts of polyethylene glycol, and 4-6 parts of propylene glycol.

[0019] The technical effect of the above technical solution is: by adjusting the ratio of the solvent (polyethylene glycol 400 / propylene glycol / purified water) in the content, the addition ratio of povidone can be controlled between 2% and 3% while ensuring that the active ingredients (acetaminophen, dextromethorphan hydrobromide or doxylamine succinate) can be completely dissolved. The prepared soft capsule sample is stored at room temperature for 2 years, and its chemical properties are stable and the quality is good; the content solution in the capsule is stable, and can still maintain a transparent and clear liquid, without recrystallization, and has a beautiful appearance.

[0020] A method for preparing the cold soft capsules comprises the following steps:

[0021] S1. Preparation of glue solution;

[0022] S2. Preparation of contents:

[0023] (1) mixing polyethylene glycol and propylene glycol and heating them to 60-80° C.; adding povidone, stirring at a temperature of 60-80° C. and a rotation speed of 300-1400 rpm until a clear solution I is obtained; adding acetaminophen and dextromethorphan hydrobromide to the clear solution I; stirring at a temperature of 60-80° C. and a rotation speed of 300-700 rpm until a clear solution II is obtained;

[0024] (2) adding doxylamine succinate to purified water, stirring at a rotation speed of 10-50 rpm until the doxylamine succinate is completely dissolved to obtain a doxylamine succinate solution;

[0025] (3) adding the doxylamine succinate solution to the clear solution II at a rotation speed of 10-25 rpm; stirring to obtain the contents while maintaining the temperature at 60-80° C. and the rotation speed at 300-700 rpm; degassing the contents under vacuum, filling with nitrogen for protection, and cooling to 25-35° C. for standby use;

[0026] S3, the glue solution of step S1 and the content of step S2 are pressed into soft capsules, and after post-processing and packaging, a cold soft capsule is obtained. Preferably, in step S1, the preparation of the glue solution specifically includes the following contents: mixing a plasticizer and purified water, heating to 60-80°C, adding gelatin and continuing to mix, and when the gelatin is completely dissolved, adding a pigment, stirring evenly, vacuum degassing, measuring viscosity, and finally obtaining a glue solution, and storing it at a temperature of 55-65°C for standby use.

[0027] Preferably, gelatin is added and mixing is continued until the temperature of the gelatin melting tank reaches 70° C. and is maintained for 20-60 minutes to completely dissolve the gelatin.

[0028] Preferably, in step S2 (3), the vacuum degassing is specifically performed as follows: degassing for 15-30 minutes while maintaining vacuum (-0.64--0.98 bar).

[0029] Preferably, in step S3, the post-processing includes drying, sorting, polishing, etc.

[0030] It can be seen from the above technical scheme that, compared with the prior art, the present invention provides a solvent system for the contents of cold soft capsules and raw cold soft capsules and a preparation method thereof, which have the following technical effects:

[0031] (1) The solvent system for the contents of the cold soft capsule provided by the present invention can ensure that the contents are a clear and transparent solution, and has low cost and good stability.

[0032] (2) The cold soft capsules obtained by using the solvent system of the present invention have stable chemical properties and good quality when stored for 2 years at room temperature; the solution of the contents in the capsules is stable and can still remain a transparent clear liquid without recrystallization and has a beautiful appearance; the cold soft capsules produced by the key process steps have high bioavailability, rapid effect, good stability, and low cost. DETAILED DESCRIPTION

[0033] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0034] The embodiment of the present invention provides a night-time compound preparation for treating colds

[0035] A solvent system for the contents of cold soft capsules comprises the following components by weight: 20-90 parts of solvent and 1-20 parts of co-solvent.

[0036] In order to further optimize the above technical solution, the solvent is selected from one or more of polyethylene glycol, propylene glycol, glycerol and water. Further, the polyethylene glycol can be selected from one or more of polyethylene glycol 200, polyethylene glycol 400 and polyethylene glycol 600.

[0037] In order to further optimize the above technical solution, the solvent is a mixture of polyethylene glycol, propylene glycol and water. Further, the polyethylene glycol can be selected from one or more of polyethylene glycol 200, polyethylene glycol 400 and polyethylene glycol 600.

[0038] In order to further optimize the above technical solution, the cosolvent is povidone. Further, the povidone is selected from one or more of povidone 12, povidone 17, povidone 25, povidone 29-32, and povidone 30.

[0039] A cold soft capsule contains the above-mentioned solvent system, and the active ingredients in the cold soft capsule are selected from one or more of acetaminophen, dextromethorphan hydrobromide, doxylamine succinate, phenylephrine hydrochloride, pseudoephedrine hydrochloride, guaifenesin glyceryl ether, diphenhydramine hydrochloride and chlorpheniramine maleate.

[0040] In order to further optimize the above technical solution, the following components are included by weight: 10-35 parts of active ingredients, 20-90 parts of solvents, and 1-20 parts of co-solvents.

[0041] In order to further optimize the above technical solution, the active ingredients are acetaminophen, dextromethorphan hydrobromide and doxylamine succinate, and the weight ratio is (25-29): (1.0-1.5): (0.4-0.6).

[0042] In order to further optimize the above technical scheme, the following components are included by weight percentage: 25-29 parts of acetaminophen, 1.0-1.5 parts of dextromethorphan hydrobromide, 0.4-0.6 parts of doxylamine succinate, 2-3 parts of povidone, 2.5-10 parts of purified water, 45-65 parts of polyethylene glycol, and 4-6 parts of propylene glycol.

[0043] A method for preparing a cold soft capsule comprises the following steps:

[0044] S1. Preparation of glue solution;

[0045] S2. Preparation of contents:

[0046] (1) mixing polyethylene glycol and propylene glycol and heating them to 60-80° C.; adding povidone, stirring at a temperature of 60-80° C. and a rotation speed of 300-1400 rpm until a clear solution I is obtained; adding acetaminophen and dextromethorphan hydrobromide to the clear solution I; stirring at a temperature of 60-80° C. and a rotation speed of 300-700 rpm until a clear solution II is obtained;

[0047] (2) adding doxylamine succinate to purified water, stirring at a rotation speed of 10-50 rpm until the doxylamine succinate is completely dissolved to obtain a doxylamine succinate solution;

[0048] (3) adding doxylamine succinate solution to the clear solution II at a rotation speed of 10-25 rpm; stirring to obtain the contents while maintaining the temperature at 60-80° C. and the rotation speed at 300-700 rpm; degassing the contents under vacuum, filling with nitrogen for protection, and cooling to 25-35° C. for standby use;

[0049] S3, the glue solution of step S1 and the content of step S2 are pressed into soft capsules, and after post-processing and packaging, the cold soft capsules are obtained. In order to further optimize the above technical scheme, in step S1, the preparation of the glue solution specifically includes the following contents: mixing the plasticizer and purified water, heating to 60-80°C, adding gelatin and continuing to mix, and when the gelatin is completely dissolved, adding the pigment, stirring evenly, vacuum degassing, measuring the viscosity, and finally obtaining the glue solution, and storing it at a temperature of 55-65°C for standby use.

[0050] In order to further optimize the above technical solution, gelatin is added and the mixture is continuously mixed until the temperature of the gelatin melting tank reaches 70°C and is maintained for 20-60 minutes to completely dissolve the gelatin.

[0051] In order to further optimize the above technical solution, in step S2 (3), the specific operation of vacuum degassing is: degassing for 15-30 minutes while maintaining vacuum (-0.64--0.98 bar).

[0052] In order to further optimize the above technical solution, in step S3, post-processing includes drying, sorting, polishing, etc.

[0053] In order to better explain the present invention, the following is described in conjunction with specific implementations:

[0054] The raw materials used in the specific embodiments, such as gelatin, glycerol, sorbitol, sorbitan solution, etc., can be purchased through conventional channels.

[0055] The embodiment of the present invention provides a night-time cold soft capsule, comprising a gelatin solution and a preparation of contents, and the two are pressed into a soft capsule, wherein the formula of the gelatin solution comprises: gelatin, glycerin, sorbitol sorbitan solution, D&C Yellow No. 10, FD&C Blue No. 1 and purified water, as shown in Table 2.

[0056] Table 2 Gelatin solution formula

[0057] Material Name ％ Purified water 30-35 Sorbitol sorbitan solution or / and sorbitol solution 10-14 glycerin 9-12 gelatin 40-45 D&C Yellow No. 10 0.01-0.1 FD&C Blue No. 1 0.01-0.05 TOTAL 100％

[0058] The content formula includes acetaminophen, dextromethorphan hydrobromide, doxylamine succinate, polyethylene glycol, propylene glycol, povidone, and purified water, as shown in Table 3

[0059] Table 3 Contents formula

[0060] Material Name ％ Acetaminophen 10-30 Dextromethorphan Hydrobromide 1-3 Doxylamine succinate 0.1-1 Polyethylene glycol 20-75 Propylene glycol 1-15 Povidone 1-20 Purified water 1-10 TOTAL 100％

[0061] Example 1

[0062] This embodiment provides a solvent system for the contents of cold soft capsules, which includes the following components by weight: 20 parts of polyethylene glycol 200, propylene glycol, glycerin and water, and 1 part of povidone K12.

[0063] Example 2

[0064] This embodiment provides a solvent system for the contents of cold soft capsules, which includes the following components by weight: 90 parts of polyethylene glycol 600, propylene glycol, glycerin and water, and 20 parts of povidone K25.

[0065] Example 3

[0066] This embodiment provides a solvent system for the contents of cold soft capsules, which includes the following components by weight: 45 parts of polyethylene glycol 400, propylene glycol and water, and 15 parts of povidone K12.

[0067] The solvent systems for the contents of the cold soft capsules disclosed in Examples 1-3 all have good stability when applied to the cold soft capsules.

[0068] Example 4

[0069] This embodiment provides a cold soft capsule that can use the solvent system of the present application, which is pressed into a soft capsule by the gelatin solution and the contents in Table 2. The specific formula of the gelatin solution can be reasonably selected by those skilled in the art within the range in Table 2, and will not be elaborated here. The content formula is shown in Table 7.

[0070] Table 7 Contents formula

[0071]

[0072] The preparation method of the cold soft capsule provided in Example 4 of the present invention comprises the following steps:

[0073] (1) Preparation of gelatin for forming capsule shell:

[0074] a. Mix the plasticizer (glycerol, sorbitol sorbitan solution or / and sorbitol solution) and purified water in a glue melting tank and heat to 60-80°C;

[0075] b. Add gelatin and continue mixing until the temperature of the gelatin melting tank reaches 70°C and maintain for 20-60 minutes to completely dissolve the gelatin;

[0076] c. Add the plain solution, stir for 10 minutes, and then degas for 5-20 minutes at a vacuum of -0.06MPa--0.10MPa to obtain a uniform color glue solution. Measure the viscosity, which is required to be 8000-25000CPs;

[0077] d. Store the glue solution at 55-65℃ for pelleting.

[0078] (2) Preparation of contents:

[0079] a. Add the weighed polyethylene glycol 400 and propylene glycol to the batching system and stir at 200-500 RPM, and start heating the mixture to 60-80 ° C;

[0080] b. When the temperature reaches 60-80°C, slowly add the weighed amount of Povidone K30. Maintain the temperature at 60-80°C and stir at 300-1400 rpm until a clear solution is obtained;

[0081] c. Maintain the temperature at 60-80°C, stir at a low speed of 10-25 rpm, and slowly add the weighed active ingredient. Maintain the temperature at 60-80°C, stir at 500±200 RPM for 60 minutes until a clear solution is obtained;

[0082] d. Slowly add the weighed other active ingredients into the purified water and stir at 10-50 rpm for 10 minutes until completely dissolved.

[0083] e. Maintain low-speed stirring at 10-25 rpm, slowly add other active ingredient solutions that have been completely dissolved, and adjust the stirring rate to 500±200 rpm, maintain the mixture temperature at 60-80°C and stir for 30 minutes to obtain a clear solution.

[0084] Note: Steps c, d and e can be reasonably adjusted according to the specific type of active ingredient.

[0085] f. Maintain vacuum (-0.64--0.98) bar, degas for 15-30 minutes, fill with nitrogen for protection after vacuum degassing, and cool the filling to 30℃.

[0086] (3) Suppression:

[0087] The contents and gelatin prepared in the above steps are pressed into soft capsules on a soft capsule machine, and then subjected to subsequent post-processing processes such as drying, sorting, polishing, etc., and finally packaged, thereby obtaining a night-time compound preparation for treating colds.

[0088] During the preparation of the cold soft capsules, those skilled in the art can reasonably adjust the process parameters such as stirring rate and temperature within the range of the above preparation method.

[0089] Examples 5-8 and Comparative Examples 1-2

[0090] The cold soft capsules provided in Examples 5-8 of the present invention and Comparative Examples 1-2 are prepared with sample solutions containing different solvents (polyethylene glycol 400 / propylene glycol / purified water) in different ratios, and the gelatin solution in Table 2 and the contents are pressed into soft capsules. The specific formula of the gelatin solution can be reasonably selected by those skilled in the art within the range in Table 2, and will not be elaborated here. The specific content formula is shown in Table 4.

[0091] Table 4 Contents formula of Examples 5-8 and Comparative Examples 1-2

[0092]

[0093] In order to further illustrate the technical effect of the present invention, the present invention also conducted physical stability studies and chemical stability studies on Examples 5-8 and Comparative Examples 1-2:

[0094] 1. Physical stability study:

[0095] Examples 5-8 and Comparative Examples 1-2 were placed in an environment with a temperature of 25°C and a humidity of 60% (25°C / 60%RH) to investigate whether the samples would recrystallize at 0 days, 1 month, 2 months, 3 months, 6 months, 12 months, and 24 months. The contents in the capsules were observed to see whether they would recrystallize. The results are shown in Table 5.

[0096] Table 5 Physical stability results of Examples 5-8 and Comparative Examples 1-2

[0097]

[0098] From the data in Table 5, it can be seen that for the formula with a propylene glycol / purified water ratio between 0.18 and 2, the contents are still clear and transparent, the solution is stable, and there is no recrystallization.

[0099] 2. Chemical stability study:

[0100] The capsules of Examples 5-8 and Comparative Examples 1-2 were placed in an environment with a temperature of 40°C and a humidity of 75% (40°C / 75%RH) and the samples were examined at 0 day, 1 month, 2 months, 3 months and 6 months. The results are shown in Table 6.

[0101] Table 6 Chemical stability results of Examples 5-8 and Comparative Examples 1-2

[0102]

[0103]

[0104] In summary, the solvent system for the contents of the cold soft capsule provided by the present invention can ensure that the contents are clear and transparent solutions, and has low cost and good stability. The cold soft capsule obtained by using the solvent system of the present invention is stored for 2 years at room temperature, and its chemical properties are stable and the quality is good; the content solution in the capsule is stable, and can still maintain a transparent and clear liquid, without recrystallization, and has a beautiful appearance; the cold soft capsule produced by the key process steps has high bioavailability, rapid effect, good stability, and low cost.

[0105] It will be apparent to those skilled in the art that many modifications and variations of the present invention are possible without departing from the spirit and scope of the present invention. It is therefore contemplated that the present invention covers modifications and variations of the present invention provided within the scope of the appended claims and their equivalents.

[0106] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A cold soft capsule, characterized in that: The cold soft capsule contains a solvent system and active ingredients, wherein the solvent system comprises the following components by weight: 20-90 parts of a solvent and 1-20 parts of a co-solvent; the solvent is a mixture of polyethylene glycol, propylene glycol and water; the dosage ratio of propylene glycol / purified water is 0.18-2; the co-solvent is povidone; the active ingredients in the cold soft capsule are acetaminophen, dextromethorphan hydrobromide and doxylamine succinate; the cold soft capsule comprises the following components by weight: 10-35 parts of the active ingredient, 20-90 parts of the solvent and 1-20 parts of the co-solvent; the weight ratio of the active ingredients acetaminophen, dextromethorphan hydrobromide and doxylamine succinate is (25-29):(1.0-1.5):(0.4-0.6).

2. The cold soft capsule according to claim 1, characterized in that The invention comprises the following components by weight percentage: 25-29 parts of acetaminophen, 1.0-1.5 parts of dextromethorphan hydrobromide, 0.4-0.6 parts of doxylamine succinate, 2-3 parts of povidone, 2.5-10 parts of purified water, 45-65 parts of polyethylene glycol and 4-6 parts of propylene glycol.

3. A method for preparing the cold soft capsule according to any one of claims 1 to 2, characterized in that: The following steps are involved: S1. Preparation of glue solution; S2. Preparation of contents: (1) mixing polyethylene glycol and propylene glycol and heating them to 60-80° C.; adding povidone, stirring at a temperature of 60-80° C. and a rotation speed of 300-1400 rpm until a clear solution I is obtained; adding acetaminophen and dextromethorphan hydrobromide to the clear solution I; stirring at a temperature of 60-80° C. and a rotation speed of 300-700 rpm until a clear solution II is obtained; (2) adding doxylamine succinate to purified water, stirring at a rotation speed of 10-50 rpm until the doxylamine succinate is completely dissolved to obtain a doxylamine succinate solution; (3) adding the doxylamine succinate solution to the clear solution II at a rotation speed of 10-25 rpm; stirring to obtain the contents while maintaining the temperature at 60-80° C. and the rotation speed at 300-700 rpm; degassing the contents under vacuum, filling with nitrogen for protection, and cooling to 25-35° C. for standby use; S3, pressing the glue solution of step S1 and the content of step S2 into soft capsules, and performing post-processing and packaging to obtain cold soft capsules.

4. The method for preparing the cold soft capsule according to claim 3, characterized in that: In step S1, the preparation of the glue solution specifically includes the following steps: mixing the plasticizer and purified water, heating to 60-80°C, adding gelatin and continuing to mix, adding pigment after the gelatin is completely dissolved, stirring evenly, vacuum degassing, measuring the viscosity, and finally obtaining the glue solution, which is stored at a temperature of 55-65°C for future use.

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