CN110613753A - Throat clearing dropping pill and preparation method thereof - Google Patents
Throat clearing dropping pill and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a throat-clearing dropping pill and a preparation method thereof, wherein artificial bezoar, refined indigo products, a licorice extract, a myrobalan extract and a substrate polyethylene glycol 6000 are prepared into a dropping pill core, menthol and borneol are used as coating layers to be coated on the dropping pill core, and then an external isolation coating layer is coated. The throat clearing dropping pill and the preparation method thereof reduce the dosage of the substrate, improve the drug loading rate, reduce the high temperature exposure of the menthol and the borneol and reduce the volatilization loss of the menthol and the borneol.
Description
Technical Field
The invention belongs to the field of traditional Chinese medicine preparations, and particularly relates to a throat clearing dropping pill and a preparation method thereof.
Background
Qingyan dropping pill is collected in volume 14 of "New drug Change Standard" and is a product released from the sixth Chinese medicine factory of Tianjin New pharmaceutical industry group GmbH. It is prepared from artificial bezoar, fructus Chebulae, indigo naturalis, Glycyrrhrizae radix, Mentholum and Borneolum Syntheticum as raw materials, and polyethylene glycol 6000 as adjuvant. The main function of the medicine is to dispel wind, clear heat, detoxify and relieve sore throat; can be used for treating wind-heat type pharyngitis, pharyngalgia, dry throat, thirst, slight aversion to wind, fever, pharyngeal swelling, and acute pharyngitis with the above symptoms.
As for the preparation method of the throat-clearing dropping pill, the ministerial standard number WS3-176(Z-25) -97(Z) describes the following preparation method: heating polyethylene glycol 6000 to melt, adding indigo naturalis, stirring, filtering, adding Glycyrrhrizae radix extract, fructus Chebulae extract, artificial bezoar, Borneolum Syntheticum, and Mentholum, stirring, mixing, sieving, keeping temperature at 90-100 deg.C, dripping into 15-20 deg.C liquid paraffin, cooling, making into dripping pill, wiping off liquid paraffin, and coating. Wherein the Glycyrrhrizae radix extract is obtained by extracting with water, precipitating with ethanol, adjusting the supernatant to pH 8-8.5 with ammonia water, recovering ethanol to obtain extract, adding water, adjusting to pH 2-3 with hydrochloric acid, precipitating, filtering, washing with water, and naturally evaporating water. The myrobalan ointment is thick ointment obtained by extracting myrobalan with water, precipitating with ethanol, and recovering ethanol from supernate.
In addition, chinese patent publication No. CN102973671A discloses a method for preparing a dripping pill for clearing heat from the throat, comprising the following steps: (1) collecting indigo naturalis, Glycyrrhrizae radix, fructus Chebulae, Mentholum, Borneolum Syntheticum, artificial bezoar and polyethylene glycol; (2) extracting fructus Chebulae with water, filtering, concentrating to obtain extract 1, precipitating with ethanol, and recovering ethanol to obtain fructus Chebulae extract; soaking indigo naturalis in hydrochloric acid aqueous solution, washing to neutrality, and oven drying to obtain refined indigo naturalis; extracting Glycyrrhrizae radix with water, filtering, concentrating to obtain extract 2, adding ethanol into extract 2, standing, collecting supernatant, adjusting pH to 8-8.5, filtering, recovering ethanol from filtrate, adding water, adjusting pH to 2-3, filtering, washing precipitate with water, and drying to obtain Glycyrrhrizae radix extract; (3) adding refined indigo naturalis and artificial bezoar into polyethylene glycol, heating to melt, sequentially adding Borneolum Syntheticum, Mentholum, Glycyrrhrizae radix extract and fructus Chebulae extract, stirring to melt, keeping temperature at 90 + -10 deg.C, dripping into liquid paraffin, methyl silicone oil or vegetable oil at 20 + -5 deg.C, and making into dripping pill.
The throat-clearing dropping pill prepared by the preparation method has large dosage of the matrix polyethylene glycol 6000 and small drug-loading rate, so that the number of pills required to be taken each time is large, and the compliance of patients is poor. In addition, in the preparation method, the volatile raw materials of the menthol and the borneol are heated and melted together with the polyethylene glycol 6000 and are kept warm at about 90 ℃, and the high-temperature operation causes more loss of the menthol and the borneol in the production process, causes inaccurate metering and influences the curative effect of the medicine to a certain extent. In order to improve the retention rate of menthol and borneol in the production and storage processes of products, cyclodextrin is mostly adopted for inclusion in the prior art at present. Although cyclodextrin inclusion helps to improve the stability of menthol and borneol during formulation and storage, the following problems also exist: due to the problem of encapsulation efficiency, the menthol and the borneol have certain loss in the inclusion process; and the taste of the included menthol and borneol is poor, so the throat clearing dropping pill is not suitable for buccal administration.
In order to overcome at least one defect of the throat clearing dropping pills in the prior art, the inventor conducts a great deal of research to prepare the throat clearing dropping pill, greatly reduce the dosage of matrix polyethylene glycol 6000, and better reserve the dosage and the taste of menthol and borneol.
Disclosure of Invention
In order to overcome at least one defect of the prior art, the invention provides a throat clearing dropping pill and a preparation method thereof, wherein artificial bezoar, refined products of indigo naturalis, a licorice extract, a myrobalan extract and a matrix polyethylene glycol 6000 are prepared into a dropping pill core, and then menthol and borneol are used as coating layers to coat the dropping pill core. In the throat clearing dropping pill, the menthol, the borneol and the matrix are not melted and dropped into the pill, but are wrapped on the inner core of the dropping pill made of other raw materials and the matrix, so that the dosage of the matrix polyethylene glycol 6000 can be greatly reduced, and the drug loading rate can be improved; meanwhile, when the coating layers of the menthol crystal and the borneol are coated, the coating can be carried out at a lower temperature, so that the volatilization loss of the menthol crystal and the borneol can be greatly reduced.
In one aspect, the invention provides a throat-clearing dropping pill, which comprises a dropping pill inner core, an intermediate medicine-containing layer and an external isolation coating layer, wherein the dropping pill inner core is prepared by artificial bezoar, refined indigo products, licorice extracts, myrobalan extracts and 6000 drops of matrix polyethylene glycol, the intermediate medicine-containing layer comprises medicine menthol and borneol and a coating material, and the external isolation coating layer is a film coating layer without medicine;
the weight parts of the raw materials and the auxiliary materials are as follows: 30-70 parts of indigo naturalis, 30-70 parts of liquorice, 20-60 parts of myrobalan, 20-60 parts of menthol, 5-20 parts of borneol, 2-10 parts of artificial bezoar and 150 parts of matrix polyethylene glycol 600050-;
preferably, the raw materials and auxiliary materials are as follows in parts by weight: 40-60 parts of indigo naturalis, 40-60 parts of liquorice, 30-50 parts of myrobalan, 30-50 parts of menthol, 8-15 parts of borneol, 4-8 parts of artificial bezoar and 120 parts of matrix polyethylene glycol 600080-;
more preferably, the weight parts of the raw materials and the auxiliary materials are as follows: 50 parts of indigo naturalis, 50 parts of liquorice, 40 parts of myrobalan, 40 parts of menthol, 10 parts of borneol, 6 parts of calculus bovis factitius and 6000100 parts of matrix polyethylene glycol.
In a specific embodiment, the coating material of the intermediate drug-containing layer is selected from one or more of polyethylene glycol 4000, polyethylene glycol 6000, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, hydroxyethyl cellulose and polyvinylpyrrolidone; polyethylene glycol 4000, polyethylene glycol 6000 or a mixture of both is preferred. Preferably, the weight ratio of drug to coating material is 1:0.5 to 1:2, preferably 1:0.5 to 1:1.5, e.g. 1:1.
In a specific embodiment, the refined natural indigo product is prepared by soaking natural indigo in a hydrochloric acid aqueous solution, washing to neutrality and drying.
In one embodiment, the licorice extract is prepared by the following method: extracting Glycyrrhrizae radix with water, concentrating the filtrate, adding ethanol, standing, collecting supernatant, adding ammonia water to adjust pH to 8-8.5, filtering, recovering ethanol, adding water and hydrochloric acid to adjust pH to 2-3, filtering, washing precipitate with water, and drying.
In a specific embodiment, the myrobalan extract is prepared by the following method: extracting fructus Chebulae with water, concentrating the filtrate, adding ethanol, standing, collecting supernatant, and recovering ethanol.
In a particular embodiment, the film coating comprises a water-soluble or alcohol-soluble film coating material, such as one or more of hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, hydroxyethyl cellulose, and polyvinylpyrrolidone, and a plasticizer, such as glycerol, propylene glycol, PEG, and the like. For example, the coating powder can be Opadry Chinese medicine coating powder or Opadry II type coating powder.
In another aspect, the present invention provides a preparation method of the above pharynx-clearing dropping pill, comprising the following steps:
refining raw materials in the step (1):
soaking indigo naturalis in a formula amount in a hydrochloric acid aqueous solution, washing to be neutral, and drying to obtain a refined product of indigo naturalis;
extracting Glycyrrhrizae radix with water, concentrating the filtrate, adding ethanol, standing, collecting supernatant, adding ammonia water to adjust pH to 8-8.5, filtering, recovering ethanol, adding water and hydrochloric acid to adjust pH to 2-3, filtering, washing precipitate with water, and drying to obtain Glycyrrhrizae radix extract;
adding water into myrobalan of formula amount for extraction, concentrating the filtrate, adding ethanol, standing, taking supernatant, and recovering ethanol to obtain myrobalan extract;
dropping the mixture into pills in the step (2):
heating and melting the substrate polyethylene glycol 6000 in the formula amount, the refined natural indigo product in the step (1) and the artificial bezoar in the formula amount, adding the licorice extract and the myrobalan extract in the step (1), mixing uniformly, preserving heat, dripping into a condensing agent, and preparing into the inner core of the dropping pill;
step (3), wrapping the middle medicine-containing layer:
dissolving the menthol, borneol and the coating material with the formula ratio by using ethanol to prepare a coating solution;
spraying the coating liquid on the inner core of the dripping pill in the step (2), and airing to obtain a semi-finished dripping pill;
step (4), coating a film coating layer:
and (4) spraying a film coating solution on the semi-finished dropping pills obtained in the step (3), and airing to obtain finished coated dropping pills.
In one embodiment, the purification of the feedstock of step (1) is carried out as follows:
taking indigo naturalis in a formula amount, adding 2-6 times of hydrochloric acid aqueous solution with volume concentration of 9% -27% by weight, soaking for 1-12 hours, washing to be neutral, and drying to obtain a refined product of indigo naturalis;
taking the liquorice with the formula amount, adding 8-12 times of water each time, carrying out reflux extraction for 2-4 times, each time for 2-4 hours, combining filtrates, concentrating to obtain clear paste with the relative density of 1.1-1.3 at 60-80 ℃, then adding ethanol until the volume concentration of the ethanol is 70% -85%, standing for 24-72 hours, taking supernatant, adding ammonia water to adjust the pH value to 8-8.5, filtering, recovering ethanol from the filtrate to obtain clear paste with the relative density of 1.1-1.3 at 60-80 ℃, adding 2-3 times of water, adjusting the pH value to 2-3 with hydrochloric acid, filtering, washing precipitates with water, and drying to obtain a liquorice extract;
adding 8-12 times of water into myrobalan in the formula amount each time, performing reflux extraction for 2-4 times for 2-4 hours each time, combining filtrates, concentrating to obtain fluid extract with relative density of 1.1-1.3 at 60-80 ℃, adding ethanol until the volume concentration of ethanol is 70-85%, standing for 24-72 hours, collecting supernatant, and recovering ethanol to obtain myrobalan extract.
In one embodiment, the dropping into pellets of step (2) is performed as follows: heating and melting the substrate polyethylene glycol 6000 in the formula amount, the refined natural indigo product in the step (1) and the artificial bezoar in the formula amount, adding the licorice extract and the myrobalan extract in the step (1), mixing uniformly, keeping the temperature at 90 +/-5 ℃, and dripping into liquid paraffin, methyl silicone oil or vegetable oil at 20 +/-5 ℃ to prepare the inner core of the dripping pill.
In one embodiment, the step (3) of wrapping the intermediate drug-containing layer is performed as follows: dissolving the menthol, the borneol and the coating material according to the formula amount by using 70-95% of ethanol to prepare a coating solution with the solid content of 20-50%; spraying the coating solution on the inner core of the dripping pill in step (2) at 20-30 deg.C, and air drying to obtain semi-finished dripping pill. The step (3) can be carried out once or more times until all the medicine-containing coating liquid is coated on the inner core of the dropping pill.
In one embodiment, the step (4) of applying the film coating layer is performed as follows: dissolving the film coating material with the formula ratio with water or ethanol to prepare coating liquid, spraying the coating liquid on the semi-finished dripping pill obtained in the step (3), and airing to obtain a finished product of the coated dripping pill. The step (4) can be carried out once or more times, so that the weight of the dropping pill is increased by 2 to 3 percent.
In another aspect, the invention provides a throat-clearing dropping pill prepared by the above preparation method.
Compared with the prior art, the throat clearing dropping pill has the following advantages: (1) the dosage of the matrix is less, and the drug-loading rate is large; (2) the menthol and the borneol are not dripped, but are coated on the inner core of the dripping pill as a medicine-containing layer, so that the high-temperature exposure is reduced, and the loss of the menthol and the borneol in the preparation process is reduced; (3) the isolation coating layer is coated outside the middle medicament-containing layer, so that the stability of the dripping pill in the storage process is improved; (4) the coating material of the middle drug-containing layer can adopt the same or similar material as the matrix of the inner core of the dripping pill, for example, polyethylene glycol 4000 or polyethylene glycol 6000 is adopted as the coating material of the middle drug-containing layer, has good compatibility with the inner core of the dripping pill, and does not influence the dissolution of the inner core drug. In addition, the preparation method of the throat clearing dropping pill is simple, and the preparation can be carried out at normal temperature when the medicine containing layer of the menthol and the borneol is wrapped, so that the loss of the medicine containing layer of the menthol and the borneol in the preparation process is reduced.
Detailed Description
The throat-clearing dropping pill and the preparation method thereof will be further described in detail with reference to the specific embodiments. It is to be understood that the following examples are only illustrative and explanatory of the present invention and should not be construed as limiting the scope of the present invention. All the technologies realized based on the above-mentioned contents of the present invention are covered in the protection scope of the present invention.
The parts of the raw materials used in the following examples are parts by weight unless otherwise specified.
Example 1: preparation of Qingyan drop pills No. 1
The present embodiment prepares a throat clearing dropping pill No. 1, which has the following formula:
the components with the formula amount are taken and prepared according to the following method:
refining raw materials in the step (1):
taking indigo naturalis of the formula amount, adding 6 times of hydrochloric acid aqueous solution with volume concentration of 21% by weight, soaking for 6 hours, washing to be neutral, and drying to obtain a refined product of the indigo naturalis;
taking liquorice with the formula amount, adding water for reflux extraction for 3 times, adding 10 times of water for the first time, adding 8 times of water for the second time and the third time, refluxing for 3 hours each time, combining filtrates, concentrating to obtain a clear paste with a relative density of 1.2 at 70 ℃, then adding ethanol until the volume concentration of ethanol is 85%, standing for 36 hours, taking supernate, adding ammonia water to adjust the pH to 8, filtering, recovering ethanol from the filtrate to obtain a clear paste with a relative density of 1.2 at 70 ℃, adding 3 times of water of the clear paste, adjusting the pH to 3 with hydrochloric acid, filtering, washing precipitates with water, and drying to obtain a liquorice extract;
adding water into myrobalan of the formula amount, carrying out reflux extraction for 3 times, adding 10 times of water by weight for the first time, adding 8 times of water by weight for the second time and the third time, carrying out reflux for 3 hours each time, combining filtrates, concentrating to obtain clear paste with the relative density of 1.2 at 70 ℃, then adding ethanol until the volume concentration of the ethanol is 80%, standing for 72 hours, taking supernatant, and recovering the ethanol to obtain the myrobalan extract.
Dropping the mixture obtained in the step (2) into pills: heating and melting the substrate polyethylene glycol 6000 with the formula amount, the refined natural indigo product in the step (1) and the artificial bezoar with the formula amount, adding the licorice extract and the myrobalan extract in the step (1), mixing uniformly, keeping the temperature at 90 +/-5 ℃, and dripping into methyl silicone oil with the temperature of 20 +/-5 ℃ to prepare the inner core of the dripping pill.
Wrapping the middle medicine-containing layer in the step (3): dissolving the menthol, the borneol and the coating material polyethylene glycol 6000 in the formula amount by using 85% ethanol by volume concentration to prepare coating liquid with the solid content of 40%; spraying the coating solution on the inner core of the dripping pill in the step (2) at 25 + -2 deg.C, and air drying to obtain semi-finished dripping pill.
The coating film coating layer in the step (4): dissolving the formula amount of Opadry II type coating powder with 70% ethanol by volume concentration to obtain coating liquid with solid content of 25%, spraying the coating liquid on the semi-finished dripping pill obtained in the step (3), and air drying to obtain the finished coated dripping pill, namely the Qingyan dripping pill No. 1.
In the preparation process of the Qingyan dropping pill No. 1, the inner core of the dropping pill is easy to form, round and proper in hardness, and is easy to wrap the medicine-containing layer and the isolating coating layer. The finished product of the Qingyan dropping pill No. 1 is round, even and smooth by naked eye observation.
Example 2: preparation of Qingyan dropping pill No. 2
In this embodiment, a throat-clearing dropping pill No. 2 is prepared, which has the following formula:
the components with the formula amount are taken and prepared according to the following method:
refining raw materials in the step (1):
taking indigo naturalis of the formula amount, adding 6 times of hydrochloric acid aqueous solution with volume concentration of 27% by weight, soaking for 4 hours, washing to be neutral, and drying to obtain a refined product of the indigo naturalis;
taking liquorice with the formula amount, adding water for reflux extraction for 2 times, adding 12 times of water for the first time, adding 10 times of water for the second time, refluxing for 3 hours each time, combining filtrates, concentrating to obtain a clear paste with a relative density of 1.2 at 70 ℃, then adding ethanol until the volume concentration of ethanol is 75%, standing for 48 hours, taking a supernatant, adding ammonia water to adjust the pH to 8.5, filtering, recovering ethanol from the filtrate to obtain a clear paste with a relative density of 1.2 at 70 ℃, adding 3 times of water of the clear paste, adjusting the pH to 3 with hydrochloric acid, filtering, washing precipitates with water, and drying to obtain a liquorice extract;
adding water into myrobalan of the formula amount, carrying out reflux extraction for 2 times, adding 12 times of water by weight for the first time, adding 10 times of water by weight for the second time, carrying out reflux for 3 hours each time, combining filtrates, concentrating to obtain clear paste with the relative density of 1.2 at 70 ℃, then adding ethanol until the volume concentration of the ethanol is 85%, standing for 48 hours, taking supernatant, and recovering the ethanol to obtain the myrobalan extract.
Dropping the mixture obtained in the step (2) into pills: heating and melting the substrate polyethylene glycol 6000 with the formula amount, the refined natural indigo product in the step (1) and the artificial bezoar with the formula amount, adding the licorice extract and the myrobalan extract in the step (1), mixing uniformly, keeping the temperature at 90 +/-5 ℃, and dripping into liquid paraffin with the temperature of 20 +/-5 ℃ to prepare the inner core of the dripping pill.
Wrapping the middle medicine-containing layer in the step (3): dissolving the menthol, the borneol and the polyethylene glycol 4000 serving as a coating material in the formula amount by using 95 volume percent of ethanol to prepare coating liquid with solid content of 50 percent; spraying the coating solution on the inner core of the dripping pill in the step (2) at 20 + -2 deg.C, and air drying to obtain semi-finished dripping pill.
The coating film coating layer in the step (4): dissolving the Opadry traditional Chinese medicine coating powder with the formula amount by using 80% ethanol by volume concentration to prepare coating liquid with the solid content of 25%, spraying the coating liquid on the semi-finished dropping pill obtained in the step (3), and airing to obtain a finished coated dropping pill, namely the Qingyan dropping pill No. 2.
In the preparation process of Qingyan dropping pill No. 2, the inner core of the dropping pill is easy to form, round and proper in hardness, and is easy to wrap the medicine-containing layer and the isolating coating layer. The finished product No. 2 throat-clearing dropping pill is round, even and smooth by visual observation.
Example 3: preparation of Qingyan drop pill No. 3
The present embodiment prepares a throat clearing dropping pill No. 3, which has the following formula:
the components with the formula amount are taken and prepared according to the following method:
refining raw materials in the step (1):
taking indigo naturalis of the formula amount, adding 6 times of hydrochloric acid aqueous solution with volume concentration of 15% by weight, soaking for 12 hours, washing to be neutral, and drying to obtain a refined product of the indigo naturalis;
taking liquorice with the formula amount, adding water for reflux extraction for 3 times, adding 10 times of water for the first time, adding 8 times of water for the second time and the third time, refluxing for 3 hours each time, combining filtrates, concentrating to obtain a clear paste with a relative density of 1.2 at 70 ℃, then adding ethanol until the volume concentration of ethanol is 70%, standing for 72 hours, taking supernate, adding ammonia water to adjust the pH to 8.5, filtering, recovering ethanol from the filtrate to obtain a clear paste with a relative density of 1.2 at 70 ℃, adding 3 times of water of the clear paste, adjusting the pH to 2 with hydrochloric acid, filtering, washing precipitates with water, and drying to obtain a liquorice extract;
adding water into myrobalan of the formula amount, carrying out reflux extraction for 3 times, adding 10 times of water by weight for the first time, adding 8 times of water by weight for the second time and the third time, carrying out reflux for 3 hours each time, combining filtrates, concentrating to obtain clear paste with the relative density of 1.2 at 70 ℃, then adding ethanol until the volume concentration of the ethanol is 70%, standing for 72 hours, taking supernatant, and recovering the ethanol to obtain the myrobalan extract.
Dropping the mixture obtained in the step (2) into pills: heating and melting the substrate polyethylene glycol 6000 with the formula amount, the refined natural indigo product in the step (1) and the artificial bezoar with the formula amount, adding the licorice extract and the myrobalan extract in the step (1), mixing uniformly, keeping the temperature at 90 +/-5 ℃, and dripping into methyl silicone oil with the temperature of 20 +/-5 ℃ to prepare the inner core of the dripping pill.
Wrapping the middle medicine-containing layer in the step (3): dissolving the menthol, borneol and coating materials polyethylene glycol 4000 and polyethylene glycol 6000 in the formula amount by using 75% ethanol by volume concentration to prepare coating liquid with the solid content of 30%; spraying the coating solution on the inner core of the dripping pill in the step (2) at 30 +/-2 ℃, and drying to obtain a semi-finished dripping pill.
The coating film coating layer in the step (4): dissolving the formula amount of Opadry II type coating powder with 70% ethanol by volume concentration to obtain coating liquid with solid content of 25%, spraying the coating liquid on the semi-finished dripping pill obtained in the step (3), and air drying to obtain the finished coated dripping pill, namely the Qingyan dripping pill No. 3.
In the preparation process of Qingyan dropping pill No. 3, the inner core of the dropping pill is easy to form, round and proper in hardness, and is easy to wrap the medicine-containing layer and the isolating coating layer. The finished product No. 3 throat-clearing dropping pill is round, even and smooth by visual observation.
Example 4: preparation of contrast Qingyan dripping pill No. 1
A contrast drop pill 1 for clearing heat from throat, its formulation is as follows:
the components with the formula amounts are taken, and the comparative heat clearing dropping pill No. 1 is prepared according to the method of the example 1 except the steps (2) and (3). The step (2) is as follows: heating and melting the substrate polyethylene glycol 6000 with the formula amount, the refined natural indigo product in the step (1) and the artificial bezoar with the formula amount, then sequentially adding the borneol, the menthol, the licorice extract in the step (1) and the myrobalan extract with the formula amount, uniformly mixing, keeping the temperature at 90 +/-5 ℃, and dripping into methyl silicone oil with the temperature of 20 +/-5 ℃ to prepare the inner core of the dropping pill. In addition, the step of wrapping the middle medicine-containing layer in the step (3) is omitted.
In the preparation process of the comparative Qingyan dripping pill No. 1, the liquid medicine is in a chain bead shape when being dripped out and is difficult to be dripped into pills. Then the dosage of the matrix polyethylene glycol 6000 is gradually increased, and the dripping condition is improved.
Example 5: preparation of contrast Qingyan dripping pill No. 2
In this example, a comparative qingyan drop pill No. 2 is prepared, which has the following formula:
the ingredients with the formula amounts are taken, and the comparative heat-clearing dropping pill No. 2 is prepared according to the method of the example 1 except the steps (2) and (3). The step (2) is as follows: heating and melting the substrate polyethylene glycol 6000 with the formula amount, the refined natural indigo product in the step (1) and the artificial bezoar with the formula amount, then sequentially adding the borneol, the menthol, the licorice extract in the step (1) and the myrobalan extract with the formula amount, uniformly mixing, keeping the temperature at 90 +/-5 ℃, and dripping into methyl silicone oil with the temperature of 20 +/-5 ℃ to prepare the inner core of the dropping pill. In addition, the step of wrapping the middle medicine-containing layer in the step (3) is omitted.
In the preparation process of the comparative Qingyan dropping pill No. 2, the inner core of the dropping pill is easy to form, round and appropriate in hardness, and is easy to be wrapped by an isolation coating layer. The finished product is compared with the Qingyan dropping pill No. 2 by naked eye observation, and the product is round, even and smooth.
Example 6: examination of dissolution time limit
Checking the dissolution time limit of the Qingyan dripping pills No. 1, No. 2 and No. 3 and the comparison Qingyan dripping pill No. 2 according to the dissolution time limit checking method under the general rule of 0108 pills in the pharmacopoeia preparation of 2015 edition. The results are shown in table 1 below.
TABLE 1 dissolution time limit results of each Qingyan drop pill
| Throat clearing dripping pill No. 1 | Throat clearing dripping pill No. 2 | No. 3 throat-clearing dropping pill | Contrast Qingyan dripping pill No. 2 | |
| Dissolving time limit (min) | 13.65±1.18 | 13.49±1.51 | 13.58±1.23 | 13.37±1.35 |
From the results, it can be seen that, compared with the comparative Qingyan drop pill No. 2 in which menthol and borneol are dropped together with other components into a pill, the dissolution of the finished drop pill is not affected basically by wrapping menthol and borneol on the inner core of the drop pill as the intermediate drug-containing layer, and the dissolution time limits of the menthol and borneol are not significantly different from each other, both can be dissolved out quickly, and meet the requirements of pharmacopoeia on the dissolution time limit of the coated drop pill.
Example 7: content determination of menthol and borneol
In order to evaluate the loss or retention of volatile components of menthol and borneol in the preparation process of the dropping pill, the content of menthol and borneol in the Qingyan dropping pill No. 1 and the comparison Qingyan dropping pill No. 2 was determined by gas chromatography.
7.1 instruments and reagents
Shimadzu GC-14B gas chromatograph, FID detector, workstation;
an ultrasonic cleaner: the power is 250W;
menthol and borneol reference substances were purchased from the chinese drug biologies institute (for content determination);
the methyl salicylate and ethyl acetate reagents are analytically pure;
no. 1 of the throat-clearing dropping pill prepared in the above example 1;
the comparative Qingyan dropping pill No. 2 prepared in the above example 5.
7.2 methods
7.2.1 chromatographic conditions: the chromatographic column is a polyethylene glycol-20M packed column, and is coated by 5 percent; the column temperature was 130 ℃; the temperature of the gasification chamber is 200 ℃; the temperature of the detector is 210 ℃; the carrier gas was nitrogen and the flow rate was 0.8 ml/min.
7.2.2 preparation of solution
Preparing an internal standard solution: an appropriate amount of methyl salicylate is precisely weighed, and ethyl acetate is added to prepare a solution with the concentration of 2.5 mg/ml.
Preparing a reference substance solution: precisely weighing appropriate amount of Borneolum and Mentholum reference substances, and adding internal standard solution to obtain solutions with concentration of 0.15mg/ml and 1.0 mg/ml.
Preparing a test solution: taking a proper amount of the Qingyan dropping pill No. 1 and the comparison Qingyan dropping pill No. 2, grinding, precisely weighing about 0.12g, placing into a 10ml measuring flask, adding a proper amount of internal standard solution for ultrasonic treatment, adding the internal standard solution for diluting to a scale after dissolving, and shaking up to obtain the Qingyan dropping pill.
Preparation of negative control solution: except that borneol and menthol are not weighed, a negative sample without borneol and menthol is prepared according to the same formula and method as the comparison No. 2 Qingyan dropping pill, and a negative control solution is prepared according to the preparation method of the test solution. And (5) injecting and recording a chromatogram, wherein the result shows that no interference peak exists in the corresponding peak positions of the borneol and the menthol in the negative sample.
7.3 determination and results
And respectively drawing standard curves by adopting menthol and borneol standards. The method has good precision, reproducibility, stability and sample recovery rate.
Precisely sucking 1 μ L of sample solution, injecting into gas chromatograph, measuring each sample in parallel for 3 times, measuring according to the above chromatographic conditions, and quantitatively calculating content according to internal standard method. The average content results for both samples are shown in table 2 below.
TABLE 2 measurement results of menthol and borneol contents
From the results, it can be seen that the throat-clearing dropping pill No. 1 of the present invention has high content of effective components menthol and borneol, and large drug-loading rate. In order to evaluate the loss or retention of the menthol and borneol in the preparation process, the contents of the menthol and borneol are respectively converted into the contents corresponding to the original medicinal materials by the following method: the total parts of the raw materials and the auxiliary materials of the Qingyan dripping pill No. 1 are 356 parts, wherein 196 parts of raw materials and 160 parts of auxiliary materials (substrate and coating material), so that the content of the menthol equivalent to the raw materials is about 121.3mg/g 356/196-220.3 mg/g, and the content of the borneol equivalent to the raw materials is about 18.5mg/g 356/196-33.6 mg/g; the total parts of the raw materials and the auxiliary materials of the Qingyan dripping pill No. 2 are 456 parts, wherein 196 parts of raw materials and 260 parts of auxiliary materials (matrix and coating materials), so that the content of the menthol equivalent to the raw materials is about 76.8mg/g 456/196-178.7 mg/g, and the content of the borneol equivalent to the raw materials is about 11.7mg/g 456/196-27.2 mg/g. The data show that in the throat clearing dropping pill, the loss of the menthol and the borneol in the preparation process is less, the effective components are well reserved, the content of the effective components is high, and the curative effect is better.
The embodiments of the present invention have been described above, but the present invention is not limited to the above embodiments. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (8)
1. A throat-clearing dropping pill is characterized by comprising a dropping pill inner core, an intermediate medicine-containing layer and an external isolation coating layer, wherein the dropping pill inner core is prepared by artificial bezoar, refined products of indigo naturalis, licorice extract, myrobalan extract and 6000 drops of matrix polyethylene glycol, the intermediate medicine-containing layer comprises medicine menthol and borneol and a coating material, and the external isolation coating layer is a film coating layer without medicine;
the weight parts of the raw materials and the auxiliary materials are as follows: 30-70 parts of indigo naturalis, 30-70 parts of liquorice, 20-60 parts of myrobalan, 20-60 parts of menthol, 5-20 parts of borneol, 2-10 parts of artificial bezoar and 150 parts of matrix polyethylene glycol 600050-;
preferably, the raw materials and auxiliary materials are as follows in parts by weight: 40-60 parts of indigo naturalis, 40-60 parts of liquorice, 30-50 parts of myrobalan, 30-50 parts of menthol, 8-15 parts of borneol, 4-8 parts of artificial bezoar and 120 parts of matrix polyethylene glycol 600080-;
more preferably, the weight parts of the raw materials and the auxiliary materials are as follows: 50 parts of indigo naturalis, 50 parts of liquorice, 40 parts of myrobalan, 40 parts of menthol, 10 parts of borneol, 6 parts of calculus bovis factitius and 6000100 parts of matrix polyethylene glycol.
2. The pharynx-clearing dropping pill according to claim 1, wherein the coating material of the middle drug-containing layer is selected from one or more of polyethylene glycol 4000, polyethylene glycol 6000, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, hydroxyethyl cellulose and polyvinylpyrrolidone; preferably polyethylene glycol 4000, polyethylene glycol 6000 or a mixture of the two; preferably, the weight ratio of drug to coating material is 1:0.5 to 1:2, preferably 1:0.5 to 1:1.5, e.g. 1:1.
3. The sore throat relieving dripping pill according to claim 1 or 2, wherein the refined natural indigo product is prepared by soaking natural indigo in hydrochloric acid aqueous solution, washing with water to neutrality, and oven drying;
the licorice extract is prepared by the following method: extracting Glycyrrhrizae radix with water, concentrating the filtrate, adding ethanol, standing, collecting supernatant, adding ammonia water to adjust pH to 8-8.5, filtering, recovering ethanol, adding water and hydrochloric acid to adjust pH to 2-3, filtering, washing precipitate with water, and drying;
the myrobalan extract is prepared by the following method: extracting fructus Chebulae with water, concentrating the filtrate, adding ethanol, standing, collecting supernatant, and recovering ethanol.
4. The method for preparing a dripping pill for clearing heat from the throat according to any one of claims 1 to 3, characterized by comprising the following steps:
refining raw materials in the step (1):
soaking indigo naturalis in a formula amount in a hydrochloric acid aqueous solution, washing to be neutral, and drying to obtain a refined product of indigo naturalis;
extracting Glycyrrhrizae radix with water, concentrating the filtrate, adding ethanol, standing, collecting supernatant, adding ammonia water to adjust pH to 8-8.5, filtering, recovering ethanol, adding water and hydrochloric acid to adjust pH to 2-3, filtering, washing precipitate with water, and drying to obtain Glycyrrhrizae radix extract;
adding water into myrobalan of formula amount for extraction, concentrating the filtrate, adding ethanol, standing, taking supernatant, and recovering ethanol to obtain myrobalan extract;
dropping the mixture into pills in the step (2):
heating and melting the substrate polyethylene glycol 6000 in the formula amount, the refined natural indigo product in the step (1) and the artificial bezoar in the formula amount, adding the licorice extract and the myrobalan extract in the step (1), mixing uniformly, preserving heat, dripping into a condensing agent, and preparing into the inner core of the dropping pill;
step (3), wrapping the middle medicine-containing layer:
dissolving the menthol, borneol and the coating material with the formula ratio by using ethanol to prepare a coating solution;
spraying the coating liquid on the inner core of the dripping pill in the step (2), and airing to obtain a semi-finished dripping pill;
step (4), coating a film coating layer:
and (4) spraying a film coating solution on the semi-finished dropping pills obtained in the step (3), and airing to obtain finished coated dropping pills.
5. The production process according to claim 4, wherein the purification of the raw material in the step (1) is carried out as follows:
taking indigo naturalis in a formula amount, adding 2-6 times of hydrochloric acid aqueous solution with volume concentration of 9% -27% by weight, soaking for 1-12 hours, washing to be neutral, and drying to obtain a refined product of indigo naturalis;
taking the liquorice with the formula amount, adding 8-12 times of water each time, carrying out reflux extraction for 2-4 times, each time for 2-4 hours, combining filtrates, concentrating to obtain clear paste with the relative density of 1.1-1.3 at 60-80 ℃, then adding ethanol until the volume concentration of the ethanol is 70% -85%, standing for 24-72 hours, taking supernatant, adding ammonia water to adjust the pH value to 8-8.5, filtering, recovering ethanol from the filtrate to obtain clear paste with the relative density of 1.1-1.3 at 60-80 ℃, adding 2-3 times of water, adjusting the pH value to 2-3 with hydrochloric acid, filtering, washing precipitates with water, and drying to obtain a liquorice extract;
adding 8-12 times of water into myrobalan in the formula amount each time, performing reflux extraction for 2-4 times for 2-4 hours each time, combining filtrates, concentrating to obtain fluid extract with relative density of 1.1-1.3 at 60-80 ℃, adding ethanol until the volume concentration of ethanol is 70-85%, standing for 24-72 hours, collecting supernatant, and recovering ethanol to obtain myrobalan extract.
6. The preparation method according to claim 4, wherein the dropping into pellets in the step (2) is carried out as follows: heating and melting the substrate polyethylene glycol 6000 in the formula amount, the refined natural indigo product in the step (1) and the artificial bezoar in the formula amount, adding the licorice extract and the myrobalan extract in the step (1), mixing uniformly, keeping the temperature at 90 +/-5 ℃, and dripping into liquid paraffin, methyl silicone oil or vegetable oil at 20 +/-5 ℃ to prepare the inner core of the dripping pill.
7. The preparation method according to claim 4, wherein the step (3) of wrapping the intermediate drug-containing layer is carried out as follows: dissolving the menthol, the borneol and the coating material according to the formula amount by using 70-95% of ethanol to prepare a coating solution with the solid content of 20-50%; spraying the coating solution on the inner core of the dripping pill in step (2) at 20-30 deg.C, and air drying to obtain semi-finished dripping pill.
8. The preparation method according to claim 4, wherein the step (4) of applying the film coating layer is carried out as follows: dissolving the film coating material with the formula ratio with water or ethanol to prepare coating liquid, spraying the coating liquid on the semi-finished dripping pill obtained in the step (3), and airing to obtain a finished product of the coated dripping pill.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102258484A (en) * | 2010-05-26 | 2011-11-30 | 董玲 | Freeze-dried excipient containing Chinese medicinal volatile component |
| CN102973671A (en) * | 2012-12-29 | 2013-03-20 | 天津中新药业集团股份有限公司第六中药厂 | Throat clearing dropping pill and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102258484A (en) * | 2010-05-26 | 2011-11-30 | 董玲 | Freeze-dried excipient containing Chinese medicinal volatile component |
| CN102973671A (en) * | 2012-12-29 | 2013-03-20 | 天津中新药业集团股份有限公司第六中药厂 | Throat clearing dropping pill and preparation method thereof |
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| CN117883501A (en) * | 2023-03-21 | 2024-04-16 | 津药达仁堂集团股份有限公司中药研究院 | Application of throat clearing drop pills in preparation of medicine for resisting new coronavirus |
| CN117883501B (en) * | 2023-03-21 | 2024-05-28 | 津药达仁堂集团股份有限公司中药研究院 | Application of throat clearing drop pills in preparation of medicine for resisting new coronavirus |
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