CN110613696A - Ergocalciferol capsule and preparation method thereof - Google Patents
Ergocalciferol capsule and preparation method thereof Download PDFInfo
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- CN110613696A CN110613696A CN201911018789.2A CN201911018789A CN110613696A CN 110613696 A CN110613696 A CN 110613696A CN 201911018789 A CN201911018789 A CN 201911018789A CN 110613696 A CN110613696 A CN 110613696A
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- A61K31/592—9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
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- A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
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Abstract
The invention discloses an ergocalciferol capsule and a preparation method thereof, and the ergocalciferol capsule comprises a capsule shell and contents, wherein the capsule shell comprises gelatin, glycerol and purified water; the content components comprise soybean oil, di-tert-butyl-p-cresol and ergocalciferol. The capsule shell further comprises pigment, and the weight percentages of the soybean oil, the di-tert-butyl-p-cresol and the ergocalciferol in the content are respectively 99.47-99.50%, 0.008-0.015% and 0.490-0.52%; the key parameters and the process are controlled to ensure that the capsule content is uniform and stable, the ergocalciferol serving as the active ingredient in the content is not easily oxidized and degraded, impurities are avoided, and the bioavailability is high.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to an ergocalciferol capsule and a preparation method thereof.
Background
Ergocalciferol (ergocalferol), also known as vitamin D2, chemical name: (3 β,5Z,7E,22E) -9,10-secoergosta-5,7,10(19),22-tetraen-3-ol, formula: C28H 44O; molecular weight: 396.65, respectively; the chemical structural formula is as follows:
the ergocalciferol is colorless needle crystal or white crystalline powder; no odor and no taste; easily go bad when exposed to light or air, and the melting point is: 119 ℃ in 119 ℃; it is very soluble in chloroform, soluble in ethanol, acetone or diethyl ether, slightly soluble in vegetable oil, and insoluble in water. Is easily affected by air and illumination, and has good heat resistance.
Ergocalciferol is used for the treatment of hypocalcemia and its clinical manifestations in patients with hypoparathyroidism, as well as for the treatment of familial hypophosphatemia (vitamin D resistant rickets); the medicine can also be used for treating nutritional rickets or osteomalacia, vitamin D dependent rickets, rickets or osteomalacia secondary to long-term high dose anticonvulsant treatment, early renal osteodystrophy, osteoporosis (combined calcium) and hypophosphatemia related to Vanconi syndrome (combined acidosis treatment).
Disclosure of Invention
The invention aims to provide an ergocalciferol capsule with uniform content and a preparation method thereof, and the preparation method can ensure the uniformity and stability of the ergocalciferol in the capsule.
In order to achieve the purpose, the invention adopts the technical scheme that:
an ergocalciferol capsule comprising a capsule shell and contents, wherein the capsule shell comprises gelatin, glycerin and purified water, and is characterized in that: the content components comprise soybean oil, di-tert-butyl-p-cresol and ergocalciferol.
Further, the content components comprise the following components in percentage by weight:
99.47 to 99.50 percent of soybean oil;
0.008 to 0.015 percent of ditertbutyl p-cresol;
0.490-0.52% ergocalciferol.
Further, the content components comprise the following components in percentage by weight: 0.008 to 0.013 percent.
Further, the capsule shell also comprises pigment.
Further, the pigment in the capsule shell component is blue pigment No.1 or/and yellow pigment No. 10.
Further, the capsule shell comprises the following components in percentage by weight:
or the capsule shell comprises the following components in percentage by weight:
or the capsule shell comprises the following components in percentage by weight:
also provides a preparation method of the ergocalciferol capsule, which comprises the following steps:
(1) preparation of contents: dividing the required soybean oil into 4 parts for later use, wherein the first part of soybean oil accounts for 91% of the required soybean oil content, and the second, third and fourth parts of soybean oil respectively account for 3% of the required soybean oil content;
a: taking a first part of soybean oil to a reaction device, and heating to 35-45 ℃ for later use;
b: b, mixing a second part of soybean oil with di-tert-butyl-p-cresol, stirring until the di-tert-butyl-p-cresol is completely dissolved to obtain a well-mixed soybean oil/di-tert-butyl-p-cresol solution, adding the soybean oil/di-tert-butyl-p-cresol solution into the soybean oil obtained in the step a, cooling to 29-35 ℃, and carrying out vacuum degassing treatment for 5-30 minutes for later use;
c: taking a third part of soybean oil and ergocalciferol, mixing and stirring the third part of soybean oil and ergocalciferol under the condition of a yellow light lamp at the temperature of 29-35 ℃ for 15-30 minutes under the protection of nitrogen to obtain a mixed soybean oil/ergocalciferol solution;
and d, mixing and stirring the solution obtained in the step a and the mixed solution obtained in the step b and the mixed solution obtained in the step c in a reaction device under the condition of a yellow light and under the protection of nitrogen, simultaneously, lubricating and washing the reaction container in the step c with fourth soybean oil, adding the solution after lubrication into the reaction device, keeping the mixing temperature at 29-35 ℃, stirring for 60-120 minutes, and degassing for 5-30 minutes to obtain a clear and transparent solution.
(2) Preparing a capsule shell:
e: weighing glycerol and purified water, mixing and stirring, and heating to 60-80 ℃; adding gelatin, and continuously stirring until the gelatin is completely dissolved, wherein the temperature is kept at 65-75 ℃ in the continuous stirring process;
f: and e, performing vacuum degassing treatment on the mixed solution obtained in the step e until the viscosity of the mixed solution is 10000-25000cps, and keeping the temperature of the glue solution at 55-65 ℃.
(3) Pelleting: and (3) pressing the content of the soft capsule prepared in the step (1) and the glue solution prepared in the step (2) on a soft capsule machine to form the soft capsule.
Further, the stirring speed in the step a is 50-100 rpm.
Further, the stirring speed in the step c is 300-500 rpm.
Further, the stirring speed in the step d is 300-500 rpm.
Due to the adoption of the technical scheme, the invention has the beneficial effects that: according to the characteristics of the ergocalciferol, the ergocalciferol with extremely poor water solubility is prepared into a soft capsule dispersed in a solvent in a molecular state, so that the bioavailability of the ergocalciferol can be obviously improved; meanwhile, the preparation process can avoid the condition of uneven content due to the fact that the ergocalciferol is small in specification and belongs to a milligram level, the risk of uneven content in the preparation process can be avoided by manufacturing the ergocalciferol into a soft capsule, and meanwhile, the stability of the ergocalciferol can be further ensured by controlling the illumination condition and the anti-oxidation treatment of the reaction in the preparation process.
Drawings
FIG. 1 is a flow diagram of a content preparation process of the present invention.
Detailed Description
The number 1 of the selected Blue pigment in the invention is FD & C Blue #1, namely FD & C Blue No. 1; yellow pigment No.10 refers to D & C Yellow #10, also referred to as D & C Yellow No. 10.
The yellow light lamp in the invention, also called anti-ultraviolet yellow safety lamp, is a yellow light lamp which adopts a unique coating, can eliminate ultraviolet rays with the wavelength of 500nm, hardly emits blue-violet light with the wavelength of less than 500nm and only contains pure yellow spectrum.
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not limiting.
Examples 1, 2, 3 and comparative example 1 were analyzed for internal stability of ergocalciferol capsules:
example 1:
preparation of capsules:
the composition of the contents is as follows:
| components | Mg/granule | Percent by weight% |
| Ergocalciferol | 1.440 | 0.505 |
| Soybean oil | 283.537 | 99.487 |
| Di-tert-butyl-p-cresol | 0.023 | 0.008 |
| Total of | 285 | 100 |
The capsule shell comprises the following components:
example 2:
preparation of capsules:
the composition of the contents is as follows:
| components | Mg/granule | Percent by weight% |
| Ergocalciferol | 1.440 | 0.505 |
| Soybean oil | 283.529 | 99.484 |
| Di-tert-butyl-p-cresol | 0.031 | 0.011 |
| Total of | 285 | 100 |
The capsule shell composition was the same as in example 1.
Example 3:
preparation of capsules:
the composition of the contents is as follows:
| components | Mg/granule | Percent by weight% |
| Ergocalciferol | 1.440 | 0.505 |
| Soybean oil | 283.524 | 99.482 |
| Di-tert-butyl-p-cresol | 0.036 | 0.013 |
| Total of | 285 | 100 |
The capsule shell composition was the same as in example 1.
Comparative example 1:
preparation of capsules:
the composition of the contents is as follows:
the capsule shell composition was the same as in example 1.
Examples 1, 2, 3 and comparative example 1 were prepared as follows:
preparation of contents:
dividing the required soybean oil into 4 parts for later use, wherein the first part of soybean oil accounts for 91 percent of the required soybean oil content, and the second part, the third part and the fourth part of soybean oil respectively account for 3 percent of the required soybean oil content:
a: taking a first equal part of soybean oil into reaction equipment, stirring at a rotating speed of 80rpm, and heating to 35-45 ℃ for later use;
b: mixing the second equal part of soybean oil with di-tert-butyl-p-cresol, stirring at the rotating speed of 300-500rpm until the di-tert-butyl-p-cresol is completely dissolved to obtain a mixed soybean oil/di-tert-butyl-p-cresol solution, adding the soybean oil/di-tert-butyl-p-cresol solution into the soybean oil obtained in the step a in the step (1), cooling to 29-35 ℃, and carrying out vacuum-pumping and degassing treatment for 20 minutes for later use;
c: taking a third equal part of soybean oil and ergocalciferol, mixing and stirring the third equal part of soybean oil and ergocalciferol for 20 minutes at the temperature of 29-35 ℃ and the rotating speed of 300-500rpm under the protection of nitrogen to obtain a well-mixed soybean oil/ergocalciferol solution;
and d, mixing and stirring the solution obtained in the step a and the mixed solution obtained in the step b and the mixed solution obtained in the step c in a reaction device under the condition of a yellow light and under the protection of nitrogen at the rotating speed of 300-500rpm, simultaneously, lubricating and washing the reaction container in the step c with a fourth part of soybean oil, adding the solution after lubrication into the reaction device, keeping the mixing temperature at 29-35 ℃, stirring for 80 minutes, and degassing for 25 minutes to obtain a clear and transparent solution.
e: weighing glycerol and purified water, mixing and stirring, and heating to 60-80 ℃; adding gelatin, continuously stirring until the gelatin is completely dissolved, wherein the stirring time is 40-50 minutes, and the temperature is maintained at 65-75 ℃ in the continuous stirring process;
f: and c, performing vacuum degassing treatment on the mixed solution obtained in the step a until the viscosity of the mixed solution is 10000-25000cps, adding a pigment into the mixed solution, stirring until the color is uniform, and keeping the temperature of the glue solution at 55-65 ℃.
(3) Pelleting: and (3) pressing the content of the soft capsule prepared in the step (1) and the glue solution prepared in the step (2) on a soft capsule machine to form a soft capsule, then carrying out subsequent post-treatment processes such as drying, sorting, polishing and the like, and finally carrying out packaging treatment to obtain the ergocalciferol soft capsule.
And (4) analyzing results:
the capsules prepared in the above embodiments are placed under the condition of 40 +/-2 ℃/75 +/-5% RH, according to the detection results, as shown in Table 1, the content of di-tert-butyl-p-cresol is within the range of 0.008% -0.013%, the detected impurities in the prepared contents are less, comparative analysis shows that the content proportion provided by the invention can prevent the ergocalciferol serving as the active ingredient from being degraded, and the stability of the contents can be ensured by adopting the composition proportion of the contents.
TABLE 1 determination of impurities in capsules
8 sets of comparative analyses were performed for homogeneity of the ergocalciferol capsule contents, where the first set: examples 4, 5, 6; second group: examples 7, 8, 9; third group: examples 10, 11, 12; and a fourth group: comparative examples 2, 3, 4; and a fifth group: examples 13, 14, 15; a sixth group: 16. 17, 18; a seventh group: 19. 20, 21; and an eighth group: comparative examples 5, 6, 7; the analysis was carried out:
the contents selected in the first to eighth groups of examples were arranged in the following ratios in the tables, and the experiments in the first to eighth groups were performed with the mass expanded by 10000 times as an example, and analyzed:
the capsule content in the following preparation method is prepared from the following components in parts by weight:
| components | Mg/granule | Each 10000 granules of the composition | Percent by weight% |
| Ergocalciferol | 1.440 | 14.4 | 0.51 |
| Soybean oil | 283.536 | 2835.36 | 99.482 |
| Di-tert-butyl-p-cresol | 0.024 | 0.24 | 0.008 |
| Total of | 285 | 2850 | 100 |
First group, examples 4, 5 and 6.
Example 4:
preparation of contents:
2835.36 soybean oil was divided into four portions for use, the first portion being 2580.1776g, the second, third and fourth portions being 85.0608 g:
step a: taking a first part of soybean oil into reaction equipment, stirring at 50-100 rpm, and heating to 35 ℃ for later use;
step b: mixing and stirring a second part of soybean oil and 0.24g of di-tert-butyl-p-cresol at the rotating speed of 350rpm until the di-tert-butyl-p-cresol is completely dissolved to obtain a mixed soybean oil/di-tert-butyl-p-cresol solution, adding the soybean oil/di-tert-butyl-p-cresol solution into the stirred soybean oil obtained in the step a in the step (1), cooling to 29 ℃, and carrying out vacuum-pumping and degassing treatment for 20 minutes for later use;
step c: mixing and stirring a third part of soybean oil and 14.4g of ergocalciferol under the condition of a yellow light and under the protection of nitrogen at the rotating speed of 350rpm for 20 minutes to obtain a mixed soybean oil/ergocalciferol solution;
and d, mixing and stirring the solution obtained in the step a and the solution obtained in the step b and the soybean oil/ergocalcific alcohol solution obtained in the step c under the condition of a yellow light lamp and under the condition of nitrogen protection at the rotating speed of 350rpm, simultaneously, lubricating and washing the reaction container in the step c by using a fourth part of soybean oil, adding the solution after lubrication into a reaction device, keeping the mixing temperature at 29 ℃, stirring for 60 minutes, and degassing for 20 minutes to obtain a clear and transparent solution.
Example 5:
the entire procedure for the preparation of the contents was as in example 4, wherein the stirring time in step d was 90 minutes.
Example 6:
the entire procedure for the preparation of the contents was as in example 4, wherein the stirring time in step d was 120 minutes.
Second group:
example 7:
preparation of contents:
2835.36 soybean oil was divided into four portions for use, the first portion being 2580.1776g, the second, third and fourth portions being 85.0608 g:
a: taking a first part of soybean oil into reaction equipment, stirring at 50-100 rpm, and heating to 40 ℃ for later use;
b: mixing and stirring a second part of soybean oil and 0.24g of di-tert-butyl-p-cresol at the rotating speed of 350rpm until the di-tert-butyl-p-cresol is completely dissolved to obtain a mixed soybean oil/di-tert-butyl-p-cresol solution, adding the mixed solution into the stirred soybean oil obtained in the step a in the step (1), cooling to 32 ℃, and carrying out vacuum-pumping and degassing treatment for 25 minutes for later use;
c: mixing and stirring a third part of soybean oil and 14.4g of ergocalciferol under the condition of a yellow light and under the protection of nitrogen at the rotating speed of 350rpm for 20 minutes to obtain a mixed soybean oil/ergocalciferol solution;
and d, mixing and stirring the solution obtained in the step a and the solution obtained in the step b and the soybean oil/ergocalcific alcohol solution obtained in the step c under the condition of a yellow light lamp and under the condition of nitrogen protection at the rotating speed of 350rpm, simultaneously, lubricating and washing the reaction container in the step c by using a fourth part of soybean oil, adding the solution after lubrication into a reaction device, keeping the mixing temperature at 32 ℃, stirring for 60min, and degassing for 25 min to obtain a clear and transparent solution.
Example 8:
the entire procedure for the preparation of the contents was as in example 7, wherein the stirring time in step d was 90 minutes.
Example 9:
the entire procedure for the preparation of the contents was as in example 7, wherein the stirring time in step d was 120 minutes.
Third group:
example 10:
preparation of contents:
2835.36 soybean oil was divided into four portions for use, the first portion being 2580.1776g, the second, third and fourth portions being 85.0608 g:
a: taking a first part of soybean oil into reaction equipment, stirring at 50-100 rpm, and heating to 45 ℃ for later use;
b: mixing and stirring a second part of soybean oil and 0.24g of di-tert-butyl-p-cresol at the rotating speed of 350rpm until the di-tert-butyl-p-cresol is completely dissolved to obtain a mixed soybean oil/di-tert-butyl-p-cresol solution, adding the mixed solution into the stirred soybean oil obtained in the step a in the step (1), cooling to 35 ℃, and carrying out vacuum-pumping and degassing treatment for 30 minutes for later use;
c: mixing and stirring a third part of soybean oil and 14.4g of ergocalciferol under the condition of a yellow light and under the protection of nitrogen at the rotating speed of 350rpm for 20 minutes to obtain a mixed soybean oil/ergocalciferol solution;
and d, mixing and stirring the solution obtained in the step a and the solution obtained in the step b and the soybean oil/ergocalcific alcohol solution obtained in the step c under the condition of a yellow light lamp and under the condition of nitrogen protection at the rotating speed of 350rpm, simultaneously, lubricating and washing the reaction container in the step c by using a fourth part of soybean oil, adding the solution after lubrication into a reaction device, keeping the mixing temperature at 35 ℃, stirring for 60min, and degassing for 30 min to obtain a clear and transparent solution.
Example 11:
the entire procedure for the preparation of the contents was as in example 10, with a stirring time of 90 minutes in step d.
Example 12:
the entire procedure for the preparation of the contents was as in example 10, wherein the stirring time in step d was 120 minutes.
And a fourth group: comparative examples 2, 3, 4:
comparative example 2:
preparation of contents:
2835.36 soybean oil was divided into four portions for use, the first portion being 2580.1776g, the second, third and fourth portions being 85.0608 g:
a: taking a first part of soybean oil into reaction equipment, stirring at 50-100 rpm, and heating to 40 ℃ for later use;
b: mixing and stirring a second part of soybean oil and 0.24g of di-tert-butyl-p-cresol at the rotating speed of 350rpm until the di-tert-butyl-p-cresol is completely dissolved to obtain a mixed soybean oil/di-tert-butyl-p-cresol solution, adding the mixed solution into the stirred soybean oil obtained in the step a in the step (1), cooling to 25 ℃, and carrying out vacuum degassing treatment for 25 minutes for later use;
c: mixing and stirring a third part of soybean oil and 14.4g of ergocalciferol under the condition of a yellow light and under the protection of nitrogen at the rotating speed of 350rpm for 20 minutes to obtain a mixed soybean oil/ergocalciferol solution;
and d, mixing and stirring the solution obtained in the step a and the solution obtained in the step b and the soybean oil/ergocalcific alcohol solution obtained in the step c under the condition of a yellow light lamp and under the condition of nitrogen protection at the rotating speed of 350rpm, simultaneously, lubricating and washing the reaction container in the step c by using a fourth part of soybean oil, adding the solution after lubrication into a reaction device, keeping the mixing temperature at 25 ℃, stirring for 60min, and degassing for 20 min to obtain a clear and transparent solution.
Comparative example 3:
the entire procedure for the preparation of the contents was the same as in comparative example 2, wherein the stirring time in step d was 90 minutes.
Comparative example 4:
the entire procedure for the preparation of the contents was the same as in comparative example 2, wherein the stirring time in step d was 120 minutes.
Taking samples at the middle position of the upper part, the edge position of the upper part, the middle position of the lower part and the edge position of the lower part of the content in the preparation tank to measure the content of the content, and inspecting whether the mixture is uniformly stirred or not; the content standard is as follows: 100 to 120 percent. The following table was analyzed for the above results:
and a fifth group:
example 13:
preparation of contents:
2835.36 soybean oil was divided into four portions for use, the first portion being 2580.1776g, the second, third and fourth portions being 85.0608 g:
a: taking a first part of soybean oil into reaction equipment, stirring at 50-100 rpm, and heating to 35 ℃ for later use;
b: mixing and stirring a second part of soybean oil and 0.24g of di-tert-butyl-p-cresol at the rotating speed of 300rpm until the di-tert-butyl-p-cresol is completely dissolved to obtain a mixed soybean oil/di-tert-butyl-p-cresol solution, adding the mixed solution into the stirred soybean oil obtained in the step a in the step (1), cooling to 32 ℃, and carrying out vacuum-pumping and degassing treatment for 20 minutes for later use;
c: mixing and stirring a third part of soybean oil and 14.4g of ergocalciferol under the condition of a yellow light and under the protection of nitrogen at the rotating speed of 300rpm for 15 minutes to obtain a mixed soybean oil/ergocalciferol solution;
and d, mixing and stirring the solution obtained in the step a and the solution obtained in the step b and the soybean oil/ergocalcific alcohol solution obtained in the step c under the condition of a yellow light lamp and under the condition of nitrogen protection at the rotating speed of 300rpm, simultaneously, lubricating and washing the reaction container in the step c by using a fourth part of soybean oil, adding the solution after lubrication into a reaction device, keeping the mixing temperature at 32 ℃, stirring for 60min, and degassing for 20 min to obtain a clear and transparent solution.
Example 14:
the entire procedure for the preparation of the contents was as in example 13, with a stirring time of 90 minutes in step d.
Example 15:
the entire procedure for the preparation of the contents was as in example 13, with a stirring time of 120 minutes in step d.
A sixth group:
example 16:
preparation of contents:
2835.36 soybean oil was divided into four portions for use, the first portion being 2580.1776g, the second, third and fourth portions being 85.0608 g:
a: taking a first part of soybean oil into reaction equipment, stirring at 50-100 rpm, and heating to 40 ℃ for later use;
b: mixing and stirring a second part of soybean oil and 0.24g of di-tert-butyl-p-cresol at the rotating speed of 400rpm until the di-tert-butyl-p-cresol is completely dissolved to obtain a mixed soybean oil/di-tert-butyl-p-cresol solution, adding the mixed solution into the stirred soybean oil obtained in the step a in the step (1), cooling to 32 ℃, and carrying out vacuum-pumping and degassing treatment for 25 minutes for later use;
c: mixing and stirring a third part of soybean oil and 14.4g of ergocalciferol under the condition of a yellow light and under the protection of nitrogen at the rotating speed of 400rpm for 20 minutes to obtain a mixed soybean oil/ergocalciferol solution;
and d, mixing and stirring the solution obtained in the step a and the solution obtained in the step b and the soybean oil/ergocalcific alcohol solution obtained in the step c under the condition of a yellow light lamp and under the condition of nitrogen protection at the rotating speed of 400rpm, simultaneously, lubricating and washing the reaction container in the step c by using a fourth part of soybean oil, adding the solution after lubrication into a reaction device, keeping the mixing temperature at 32 ℃, stirring for 60min, and degassing for 25 min to obtain a clear and transparent solution.
Example 17:
the entire procedure for the preparation of the contents was as in example 16, with a stirring time of 90 minutes in step d.
Example 18:
the entire procedure for the preparation of the contents was as in example 16, wherein the stirring time in step d was 120 minutes.
A seventh group:
example 19:
preparation of contents:
2835.36 soybean oil was divided into four portions for use, the first portion being 2580.1776g, the second, third and fourth portions being 85.0608 g:
a: taking a first part of soybean oil into reaction equipment, stirring at 50-100 rpm, and heating to 40 ℃ for later use;
b: mixing and stirring a second part of soybean oil and 0.24g of di-tert-butyl-p-cresol at the rotating speed of 500rpm until the di-tert-butyl-p-cresol is completely dissolved to obtain a mixed soybean oil/di-tert-butyl-p-cresol solution, adding the mixed solution into the stirred soybean oil obtained in the step a in the step (1), cooling to 32 ℃, and carrying out vacuum-pumping and degassing treatment for 25 minutes for later use;
c: mixing and stirring a third part of soybean oil and 14.4g of ergocalciferol under the condition of a yellow light and under the protection of nitrogen at the rotating speed of 500rpm for 20 minutes to obtain a mixed soybean oil/ergocalciferol solution;
and d, mixing and stirring the solution obtained in the step a and the solution obtained in the step b and the soybean oil/ergocalcific alcohol solution obtained in the step c under the condition of a yellow light lamp and under the condition of nitrogen protection at the rotating speed of 500rpm, simultaneously, lubricating and washing the reaction container in the step c by using a fourth part of soybean oil, adding the solution after lubrication into a reaction device, keeping the mixing temperature at 32 ℃, stirring for 60min, and degassing for 25 min to obtain a clear and transparent solution.
Example 20:
the entire procedure for the preparation of the contents was as in example 19, with a stirring time of 90 minutes in step d.
Example 21:
the entire procedure for the preparation of the contents was as in example 19, with a stirring time of 120 minutes in step d.
And an eighth group:
comparative example 5:
preparation of contents:
2835.36 soybean oil was divided into four portions for use, the first portion being 2580.1776g, the second, third and fourth portions being 85.0608 g:
a: taking a first part of soybean oil to a reaction device, stirring at 50-100 rpm, and heating to 35-45 ℃ for later use;
b: mixing and stirring a second part of soybean oil and 0.24g of di-tert-butyl-p-cresol at the rotating speed of 200rpm until the di-tert-butyl-p-cresol is completely dissolved to obtain a mixed soybean oil/di-tert-butyl-p-cresol solution, adding the mixed solution into the stirred soybean oil obtained in the step a in the step (1), cooling to 29 ℃, and carrying out vacuum-pumping and degassing treatment for 25 minutes for later use;
c: mixing and stirring a third part of soybean oil and 14.4g of ergocalciferol under the condition of a yellow light and under the protection of nitrogen at the rotating speed of 200rpm for 20 minutes to obtain a mixed soybean oil/ergocalciferol solution;
and d, mixing and stirring the solution obtained in the step a and the solution obtained in the step b and the soybean oil/ergocalcific alcohol solution obtained in the step c under the condition of a yellow light lamp and under the condition of nitrogen protection at the rotating speed of 200rpm, simultaneously, lubricating and washing the reaction container in the step c by using a fourth part of soybean oil, adding the solution after lubrication into a reaction device, keeping the mixing temperature at 32 ℃, stirring for 60min, and degassing for 20 min to obtain a clear and transparent solution.
Comparative example 6:
the entire procedure for the preparation of the contents was the same as in comparative example 5, wherein the stirring time in step d was 90 minutes.
Comparative example 7:
the entire procedure for the preparation of the contents was the same as in comparative example 5, wherein the stirring time in step d was 120 minutes.
Taking samples at the middle position of the upper part, the edge position of the upper part, the middle position of the lower part and the edge position of the lower part of the content in the preparation tank to measure the content of the content, and inspecting whether the mixture is uniformly stirred or not; the content standard is as follows: 100 to 120 percent. The following table was analyzed for the above results:
according to the analysis of the results in the first to eighth groups, it can be observed from the data that the uniformity of the content can be maintained and the bioavailability of the capsule can be improved under the protection of the yellow light lamp and the protection of nitrogen gas, and under the condition that the mixing temperature is 29-35 ℃ and the rotation speed of the content is 300-500 rpm.
For the content effective substance ergocalciferol susceptible to degradation, the content prepared in example 4 was subjected to a light test (under a nitrogen-filled condition) under a light condition, and the test data is as follows:
the ergocalciferol was examined for changes in impurities after 3 days at 4500Lux as follows:
| item | Start of | 1 day | 3 days |
| Vitamin D4 | 0.76％ | 0.76％ | 0.77％ |
| Photodegradation of impurities (Single unknown impurity) | 0 | 1.94％ | 3.10％ |
The ergocalciferol capsules prepared in example 4 were placed under 4500Lux for 3 days to examine the variation of impurities in ergocalciferol, as follows:
| item | Start of | 3 days |
| Vitamin D4 | 0.76 | 0.78 |
| Photodegradation of impurities (Single unknown impurity) | 0 | 0.19 |
The content and the capsule prepared by the product can generate photodegradation impurities under the illumination condition, the contact between the content and a fluorescent lamp is particularly avoided in the production process, and a yellow lamp can be selected in the preparation process.
It will be understood by those skilled in the art that the foregoing is only a preferred embodiment of the present invention, and is not intended to limit the invention, and that any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (10)
1. An ergocalciferol capsule comprising a capsule shell and contents, wherein the capsule shell comprises gelatin, glycerin and purified water, and is characterized in that: the content components comprise soybean oil, di-tert-butyl-p-cresol and ergocalciferol.
2. The ergocalciferol capsule formulation as claimed in claim 1, characterized in that: the content components comprise the following components in percentage by weight:
99.47 to 99.50 percent of soybean oil;
0.008 to 0.015 percent of ditertbutyl p-cresol;
0.490-0.52% ergocalciferol.
3. The ergocalciferol capsule formulation as claimed in claim 2, characterized in that: the weight percentage of the ditert-butyl-p-cresol in the content components is as follows: 0.008 to 0.013 percent.
4. The ergocalciferol capsule formulation as claimed in claim 1, 2 or 3, wherein: the capsule shell further comprises a pigment.
5. The ergocalciferol capsule formulation as claimed in claim 4, wherein: the pigment in the capsule shell component is blue pigment No.1 or/and yellow pigment No. 10.
6. The ergocalciferol capsule formulation as claimed in claim 5, characterized in that: the capsule shell component
Or the capsule shell comprises the following components in percentage by weight:
or the capsule shell comprises the following components in percentage by weight:
7. a process for the preparation of ergocalciferol capsules according to claims 1, 2 or 3, characterized by comprising the following steps:
(1) preparation of contents: dividing the required soybean oil into 4 parts for later use, wherein the first part of soybean oil accounts for 91% of the required soybean oil content, and the second, third and fourth parts of soybean oil respectively account for 3% of the required soybean oil content;
a: taking a first part of soybean oil to a reaction device, and heating to 35-45 ℃ for later use;
b: b, mixing a second part of soybean oil with di-tert-butyl-p-cresol, stirring until the di-tert-butyl-p-cresol is completely dissolved to obtain a well-mixed soybean oil/di-tert-butyl-p-cresol solution, adding the soybean oil/di-tert-butyl-p-cresol solution into the soybean oil obtained in the step a, cooling to 29-35 ℃, and carrying out vacuum degassing treatment for 5-30 minutes for later use;
c: taking a third part of soybean oil and ergocalciferol, mixing and stirring the third part of soybean oil and ergocalciferol under the condition of a yellow light lamp at the temperature of 29-35 ℃ for 15-30 minutes under the protection of nitrogen to obtain a mixed soybean oil/ergocalciferol solution;
and d, mixing and stirring the solution obtained in the step a and the mixed solution obtained in the step b and the mixed solution obtained in the step c in a reaction device under the condition of a yellow light and under the protection of nitrogen, simultaneously, lubricating and washing the reaction container in the step c with fourth soybean oil, adding the solution after lubrication into the reaction device, keeping the mixing temperature at 29-35 ℃, stirring for 60-120 minutes, and degassing for 5-30 minutes to obtain a clear and transparent solution.
(2) Preparing a capsule shell:
e: weighing glycerol and purified water, mixing and stirring, and heating to 60-80 ℃; adding gelatin, and continuously stirring until the gelatin is completely dissolved, wherein the temperature is kept at 65-75 ℃ in the continuous stirring process;
f: and e, performing vacuum degassing treatment on the mixed solution obtained in the step e until the viscosity of the mixed solution is 10000-25000cps, and keeping the temperature of the glue solution at 55-65 ℃.
(3) Pelleting: and (3) pressing the content of the soft capsule prepared in the step (1) and the glue solution prepared in the step (2) on a soft capsule machine to form the soft capsule.
8. A process for the preparation of ergocalciferol capsules as claimed in claim 7, characterized in that: the stirring speed in the step d is 300-500 rpm.
9. A process for the preparation of ergocalciferol capsules according to claim 7 or 8, characterized in that: the stirring speed in the step c is 300-500 rpm.
10. A process for the preparation of ergocalciferol capsules as claimed in claim 9, characterized in that: the stirring speed in the step a is 50-100 rpm.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1823764A (en) * | 2006-03-27 | 2006-08-30 | 重庆医药工业研究院有限责任公司 | Medicinal composition containing strontium fuminate and vitamin D |
| CN101536993A (en) * | 2009-04-21 | 2009-09-23 | 浙江花园生物高科股份有限公司 | Vitamin D3 microcapsule and preparation method thereof |
| CN105030662A (en) * | 2015-06-04 | 2015-11-11 | 永信药品工业(昆山)有限公司 | Lipid-soluble vitamin D2 medicine composition and preparation method thereof |
| CN105311037A (en) * | 2014-07-31 | 2016-02-10 | 山东达因海洋生物制药股份有限公司 | Vitamin D capsule type drops and preparation method thereof |
| CN106890338A (en) * | 2017-02-24 | 2017-06-27 | 广州艾格生物科技有限公司 | A kind of vitamin D class preparation containing squalene plant oil |
| CN109662953A (en) * | 2019-02-18 | 2019-04-23 | 威海金思力生物科技股份有限公司 | A kind of vitamin D soft capsule and preparation method thereof |
| CN110313618A (en) * | 2019-06-13 | 2019-10-11 | 深圳保时健生物工程有限公司 | A kind of vitamin D2The preparation method of microcapsules |
-
2019
- 2019-10-24 CN CN201911018789.2A patent/CN110613696B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1823764A (en) * | 2006-03-27 | 2006-08-30 | 重庆医药工业研究院有限责任公司 | Medicinal composition containing strontium fuminate and vitamin D |
| CN101536993A (en) * | 2009-04-21 | 2009-09-23 | 浙江花园生物高科股份有限公司 | Vitamin D3 microcapsule and preparation method thereof |
| CN105311037A (en) * | 2014-07-31 | 2016-02-10 | 山东达因海洋生物制药股份有限公司 | Vitamin D capsule type drops and preparation method thereof |
| CN105030662A (en) * | 2015-06-04 | 2015-11-11 | 永信药品工业(昆山)有限公司 | Lipid-soluble vitamin D2 medicine composition and preparation method thereof |
| CN106890338A (en) * | 2017-02-24 | 2017-06-27 | 广州艾格生物科技有限公司 | A kind of vitamin D class preparation containing squalene plant oil |
| CN109662953A (en) * | 2019-02-18 | 2019-04-23 | 威海金思力生物科技股份有限公司 | A kind of vitamin D soft capsule and preparation method thereof |
| CN110313618A (en) * | 2019-06-13 | 2019-10-11 | 深圳保时健生物工程有限公司 | A kind of vitamin D2The preparation method of microcapsules |
Non-Patent Citations (3)
| Title |
|---|
| 傅超美等主编: "《中药药剂学》", 31 August 2014, 中国医药科技出版社 * |
| 李强等: "维生素D2微囊的制备与研究", 《食品与发酵工业》 * |
| 王生寿等主编: "《新编临床药理及药物应用》", 31 March 2019, 吉林科学技术出版社 * |
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