CN109172626B - Wild chrysanthemum injection and preparation method thereof - Google Patents
Wild chrysanthemum injection and preparation method thereof Download PDFInfo
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Abstract
The invention relates to the technical field of pharmaceutical preparations, in particular to a wild chrysanthemum injection and a preparation method thereof. The preparation method comprises the following steps: a, adding water into wild chrysanthemum for distillation to obtain distillate and distillation residue; redistilling the distillate to obtain redistillate; b, filtering the distillation residues, adding water into the residues, decocting for 1-2 times, filtering, mixing the filtrate and the decoction, and concentrating to obtain fluid extract; c, carrying out secondary alcohol precipitation treatment on the clear paste, adjusting the pH value of the filtrate to 7.0-8.5, refrigerating, filtering, collecting the filtrate, and removing ethanol until the filtrate has no alcohol smell; adding water, cooling, filtering, adjusting pH of the filtrate to 2-5, heating to 100-; d, filtering the filtrate, mixing, adding polysorbate 80 and an isoosmotic adjusting agent, adjusting the pH to 7.0-8.5, adding water to a specified amount, and filtering to obtain the compound. The preparation method solves the technical problems of poor quality stability and low percent of pass of wild chrysanthemum injection products in the prior art.
Description
Technical Field
The invention relates to the technical field of pharmaceutical preparations, in particular to a wild chrysanthemum injection and a preparation method thereof.
Background
The flos Chrysanthemi Indici injection has effects of clearing heat and detoxicating, and can be used for treating exogenous febrile disease, conjunctival congestion, swelling and pain, and throat pain; upper respiratory tract infection and acute tonsillitis belong to the upper attack of toxic heat.
A preparation method of flos Chrysanthemi Indici injection loaded in current standard (WS-11041(ZD-1041) -2002) of flos Chrysanthemi Indici injection is provided.
However, the quality of the wild chrysanthemum injection prepared by adopting the process in the prior art is unstable, the proportion of visible foreign matters is high, and even the product quality is unqualified; and the sample qualification rate is low.
In view of the above, the present invention is particularly proposed.
Disclosure of Invention
The invention aims to provide a preparation method of a wild chrysanthemum injection, and aims to solve the technical problems of poor quality stability and low percent of pass of the wild chrysanthemum injection prepared in the prior art.
The second purpose of the invention is to provide a wild chrysanthemum injection which has good quality stability and good clarity of the liquid medicine, and meets the detection requirements of the wild chrysanthemum injection under the items of WS-11041(ZD-1041) -2002 which is the current standard and the injection in pharmacopoeia of the people's republic of China.
In order to achieve the above purpose of the present invention, the following technical solutions are adopted:
a preparation method of wild chrysanthemum injection comprises the following steps:
(a) distilling flos Chrysanthemi Indici with water to obtain distillate and distillation residue; redistilling the distillate to obtain redistillate, refrigerating, and filtering;
(b) filtering the distillation residue of step (a) to obtain decoction and solid residue, decocting the residue in water for 1-2 times, filtering, mixing the filtrate and the decoction, and concentrating to obtain fluid extract;
(c) performing secondary alcohol precipitation treatment on the fluid extract, collecting filtrate, adjusting the pH of the filtrate to 7.0-8.5, refrigerating, filtering, collecting filtrate, and removing ethanol until the filtrate has no alcohol smell; adding water to make 1mL solution contain 1.0-2.0g crude drug, cooling, filtering, adjusting pH of the filtrate to 2-5, heating to 100-;
(d) ultrafiltering the filtrates in the steps (a) and (c), mixing, adding polysorbate 80 and an isoosmotic adjusting agent, adjusting the pH to 7.0-8.5, adding water to a specified amount, and filtering to obtain the final product.
According to the preparation method, the pH value is adjusted after the wild chrysanthemum is subjected to alcohol precipitation, so that the precipitation and removal of components such as acidity and tannin are promoted, and the clarity of the liquid medicine is improved; after the pH value is adjusted to 2-5, the filtrate is heated to high temperature to destroy the stability of colloid in the filtrate, and the colloid in the solution is removed through low-temperature sedimentation to improve the stability of the liquid medicine; meanwhile, the stability of the effective component chlorogenic acid is improved by pre-adjusting the pH value to be within the range of 2-5 during high-temperature heat treatment; the filtrate is treated by adopting an ultrafiltration mode, so that macromolecular substances and micromolecular impurities which are easily associated to form the macromolecular substances can be removed, the stability and the clarity of the prepared wild chrysanthemum injection are further improved, and the product quality is improved.
Wherein the solid residue is obtained by filtering the distillation residue obtained in the step (a), the collected solid is the solid residue, and the filtrate is the decoction.
Preferably, in the step (c), the second alcohol precipitation treatment comprises: adding ethanol into the fluid extract to make ethanol content reach 60-85%, refrigerating, filtering, concentrating the filtrate to obtain fluid extract, adding ethanol to make ethanol content reach 60-85%, refrigerating, and filtering.
Preferably, the relative density of the clear paste obtained in the step (b) is 1.20-1.24(40-70 ℃); in the step (c), the relative density of the clear paste obtained by concentrating the clear paste after primary alcohol precipitation is 1.18-1.22(40-70 ℃).
Preferably, the clear paste is subjected to secondary alcohol precipitation treatment, filtrate is collected, and the pH value of the filtrate is adjusted to 8.0-8.5; preferably 8.5.
As in the different examples, the pH of the filtrate may be adjusted to 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, and so on.
By adjusting the pH value after the secondary alcohol precipitation to be within the range, refrigerating and filtering, most macromolecular substances and partial calculation components can be removed, and the product quality is improved. If the temperature is directly increased after the pH is adjusted to 7.0-8.5, chlorogenic acid is decomposed by heating, and the content of effective components is reduced.
Preferably, in step (c), the pH of the filtrate is adjusted to 7.0-8.5 with sodium hydroxide solution.
Preferably, in step (c), the pH of the filtrate is adjusted to 2-5, heated to 100-115 ℃ and kept for 0.5-1.5h, then refrigerated and filtered. More preferably, heating to 110-; keeping for 1 h.
Preferably, in step (c), the pH of the filtrate is adjusted to 2-5 using a hydrochloric acid solution. For example, a 20% hydrochloric acid solution may be used.
After the pH value is adjusted to 2-5, the solution is heated to a specific temperature, the stability of the colloid can be effectively destroyed by matching the pH value and the temperature, and the colloid in the solution is removed. Under the condition that the temperature is 110 ℃ and the treatment is carried out for 1h, the colloid removing effect is optimal, and the product percent of pass can be effectively considered.
Preferably, in step (d), the ultrafiltration treatment has a molecular weight cut-off of 5kD to 50kD, preferably 10 kD.
The ultrafiltration membrane with the molecular weight cutoff is adopted for ultrafiltration treatment, so that macromolecular substances in the liquid medicine and micromolecular impurities which are easily associated into the macromolecular substances can be removed, the removal of effective components is avoided, and the clarity, the product percent of pass and the like are considered.
Preferably, the adsorbent is activated carbon. More preferably, the amount of activated carbon added to the filtrate is 0.1 to 0.5g/100mL, preferably 0.3g/100 mL.
Preferably, after the adsorbent is added, the mixture is heated to 80-100 ℃ and kept for 30-60 min. More preferably, after the addition of the adsorbent, the mixture is heated to 100 ℃ and maintained for 30 min.
Preferably, the adsorbent is added and then heated to 80-100 ℃ and filtered at 60-80 ℃. More preferably, filtration is carried out at 80 ℃.
Preferably, the isotonicity adjusting agent includes sodium chloride.
Preferably, in step (d), water is added to a predetermined amount, filtered, filled, and sterilized.
The invention also provides a wild chrysanthemum injection prepared by the preparation method.
The wild chrysanthemum injection prepared by the invention is accelerated at 40 ℃ for 6 months and is placed at 25 ℃ for 18 months, the clarity of the liquid medicine is good, and the detection requirements of the wild chrysanthemum injection under the items of WS-11041(ZD-1041) -2002 which is the current standard and the injection in pharmacopoeia of the people's republic of China are met.
Compared with the prior art, the invention has the beneficial effects that:
(1) according to the preparation method of the wild chrysanthemum injection, the secondary alcohol solution of wild chrysanthemum is used for adjusting the pH value, promoting removal of components such as acidity and tannin, and improving the clarity of the liquid medicine; after the pH value is adjusted to 2-5, the filtrate is heated to high temperature to destroy the stability of colloid in the filtrate, and the colloid in the solution is removed through low-temperature sedimentation to improve the stability of the liquid medicine; the filtrate is treated in an ultrafiltration mode, so that macromolecular substances and micromolecular impurities which are easily associated to form the macromolecular substances can be removed, the stability and the clarity of the prepared wild chrysanthemum injection are further improved, and the product quality is improved;
(2) the wild chrysanthemum injection has good quality stability and good clarity of liquid medicine, and meets the detection requirements of the wild chrysanthemum injection under the items of WS-11041(ZD-1041) -2002 which is the current standard and the injection in pharmacopoeia of the people's republic of China.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the following detailed description, but those skilled in the art will understand that the following described examples are some, not all, of the examples of the present invention, and are only used for illustrating the present invention, and should not be construed as limiting the scope of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
Example 1
The preparation method of the wild chrysanthemum injection comprises the following steps:
(1) soaking 1kg of wild chrysanthemum in 10kg of water, distilling with steam, and collecting a primary distillation liquid 1000mL and a distillation residue; redistilling the obtained primary distillate to obtain 500mL of redistillate;
(2) filtering the distillation residue obtained in the step (a) to obtain decoction and solid dregs, adding 6kg of water into the dregs, decocting for 2 times, each time for 1h, filtering, combining the filtrate and the decoction, and concentrating to obtain clear paste with the relative density of 1.22(40 ℃);
(3) adding ethanol into the fluid extract to make ethanol content reach 65% (volume fraction), refrigerating for 48h, filtering, collecting filtrate, recovering ethanol from filtrate until filtrate has no alcohol smell, concentrating the filtrate to fluid extract with relative density of 1.20(40 deg.C), adding ethanol to make ethanol content reach 85% (volume fraction), refrigerating for 24h, filtering, collecting filtrate, adding 40% sodium hydroxide solution to adjust pH of the filtrate to 8.5, refrigerating for 12h, filtering, recovering ethanol from filtrate until filtrate has no alcohol smell, adding water to 500mL, refrigerating for 36h, filtering, collecting filtrate, adding 20% hydrochloric acid solution to adjust pH of the filtrate to 2.0-3.0, heating to 110 deg.C, maintaining for 1h, cooling to room temperature, refrigerating for 24h, filtering, collecting filtrate, adding 1g active carbon into the filtrate, boiling for 30min, cooling to 80 deg.C, filtering, collecting the filtrate, refrigerating for 24h, filtering again, and collecting the filtrate;
(4) and (3) carrying out ultrafiltration treatment on the double distillate obtained in the step (1) and the filtrate finally obtained in the step (3), mixing, adding 5mL of polysorbate 80, adding 7g of sodium chloride, stirring for dissolving, adjusting the pH to 7.6 by using a sodium hydroxide solution with the mass fraction of 20%, adding water for injection to 1000mL, filtering, filling and sealing, and sterilizing to obtain the injection.
Example 2
The preparation method of the wild chrysanthemum injection comprises the following steps:
(1) soaking 1kg of wild chrysanthemum in 10kg of water, distilling with steam, and collecting a primary distillation liquid 1000mL and a distillation residue; redistilling the obtained primary distillate to obtain 500mL of redistillate;
(2) filtering the distillation residue obtained in the step (a) to obtain decoction and solid dregs, adding 6kg of water into the dregs, decocting for 2 times, each time for 1h, filtering, combining the filtrate and the decoction, and concentrating to obtain clear paste with the relative density of 1.22(40 ℃);
(3) adding ethanol into the fluid extract to make ethanol content reach 65% (volume fraction), refrigerating for 48h, filtering, collecting filtrate, recovering ethanol from filtrate until filtrate has no alcohol smell, concentrating the filtrate to fluid extract with relative density of 1.20(40 deg.C), adding ethanol to make ethanol content reach 85% (volume fraction), refrigerating for 24h, filtering, collecting filtrate, adding 40% sodium hydroxide solution to adjust pH of the filtrate to 7.0, refrigerating for 12h, filtering, recovering ethanol from filtrate until filtrate has no alcohol smell, adding water to 500mL, refrigerating for 36h, filtering, collecting filtrate, adding 20% hydrochloric acid solution to adjust pH of the filtrate to 2.0-3.0, heating to 110 deg.C, maintaining for 1h, cooling to room temperature, refrigerating for 24h, filtering, collecting filtrate, adding 1g active carbon into the filtrate, boiling for 30min, cooling to 80 deg.C, filtering, collecting the filtrate, refrigerating for 24h, filtering again, and collecting the filtrate;
(4) and (3) carrying out ultrafiltration treatment on the double distillate obtained in the step (1) and the filtrate finally obtained in the step (3), mixing, adding 5mL of polysorbate 80, adding 7g of sodium chloride, stirring for dissolving, adjusting the pH to 7.6 by using a sodium hydroxide solution with the mass fraction of 20%, adding water for injection to 1000mL, filtering, filling and sealing, and sterilizing to obtain the injection.
Example 3
The preparation method of the wild chrysanthemum injection comprises the following steps:
(1) soaking 1kg of wild chrysanthemum in 10kg of water, distilling with steam, and collecting a primary distillation liquid 1000mL and a distillation residue; redistilling the obtained primary distillate to obtain 500mL of redistillate;
(2) filtering the distillation residue obtained in the step (a) to obtain decoction and solid dregs, adding 6kg of water into the dregs, decocting for 2 times, each time for 1h, filtering, combining the filtrate and the decoction, and concentrating to obtain clear paste with the relative density of 1.22(40 ℃);
(3) adding ethanol into the fluid extract to make ethanol content reach 65% (volume fraction), refrigerating for 48h, filtering, collecting filtrate, recovering ethanol from filtrate until filtrate has no alcohol smell, concentrating the filtrate to fluid extract with relative density of 1.20(40 deg.C), adding ethanol to make ethanol content reach 85% (volume fraction), refrigerating for 24h, filtering, collecting filtrate, adding 40% sodium hydroxide solution to adjust pH of the filtrate to 8.0, refrigerating for 12h, filtering, recovering ethanol from filtrate until filtrate has no alcohol smell, adding water to 500mL, refrigerating for 36h, filtering, collecting filtrate, adding 20% hydrochloric acid solution to adjust pH of the filtrate to 2.0-3.0, heating to 110 deg.C, maintaining for 1h, cooling to room temperature, refrigerating for 24h, filtering, collecting filtrate, adding 1g active carbon into the filtrate, boiling for 30min, cooling to 80 deg.C, filtering, collecting the filtrate, refrigerating for 24h, filtering again, and collecting the filtrate;
(4) and (3) carrying out ultrafiltration treatment on the double distillate obtained in the step (1) and the filtrate finally obtained in the step (3), mixing, adding 5mL of polysorbate 80, adding 7g of sodium chloride, stirring for dissolving, adjusting the pH to 7.6 by using a sodium hydroxide solution with the mass fraction of 20%, adding water for injection to 1000mL, filtering, filling and sealing, and sterilizing to obtain the injection.
Example 4
The preparation method of the wild chrysanthemum injection comprises the following steps:
(1) soaking 1kg of wild chrysanthemum in 10kg of water, distilling with steam, and collecting a primary distillation liquid 1000mL and a distillation residue; redistilling the obtained primary distillate to obtain 500mL of redistillate;
(2) filtering the distillation residue obtained in the step (a) to obtain decoction and solid dregs, adding 6kg of water into the dregs, decocting for 2 times, each time for 1h, filtering, combining the filtrate and the decoction, and concentrating to obtain clear paste with the relative density of 1.22(40 ℃);
(3) adding ethanol into the fluid extract to make ethanol content reach 65% (volume fraction), refrigerating for 48h, filtering, collecting filtrate, recovering ethanol from filtrate until filtrate has no alcohol smell, concentrating the filtrate to fluid extract with relative density of 1.20(40 deg.C), adding ethanol to make ethanol content reach 85% (volume fraction), refrigerating for 24h, filtering, collecting filtrate, adding 40% sodium hydroxide solution to adjust pH of the filtrate to 8.5, refrigerating for 12h, filtering, recovering ethanol from filtrate until filtrate has no alcohol smell, adding water to 500mL, refrigerating for 36h, filtering, collecting filtrate, adding 20% hydrochloric acid solution to adjust pH of the filtrate to 4.0-5.0, heating to 110 deg.C, maintaining for 1h, cooling to room temperature, refrigerating for 24h, filtering, collecting filtrate, adding 1g active carbon into the filtrate, boiling for 30min, cooling to 80 deg.C, filtering, collecting the filtrate, refrigerating for 24h, filtering again, and collecting the filtrate;
(4) and (3) carrying out ultrafiltration treatment on the double distillate obtained in the step (1) and the filtrate finally obtained in the step (3), mixing, adding 5mL of polysorbate 80, adding 7g of sodium chloride, stirring for dissolving, adjusting the pH to 7.6 by using a sodium hydroxide solution with the mass fraction of 20%, adding water for injection to 1000mL, filtering, filling and sealing, and sterilizing to obtain the injection.
Example 5
The preparation method of the wild chrysanthemum injection comprises the following steps:
(1) soaking 1kg of wild chrysanthemum in 10kg of water, distilling with steam, and collecting a primary distillation liquid 1000mL and a distillation residue; redistilling the obtained primary distillate to obtain 500mL of redistillate;
(2) filtering the distillation residue obtained in the step (a) to obtain decoction and solid dregs, adding 6kg of water into the dregs, decocting for 2 times, each time for 1h, filtering, combining the filtrate and the decoction, and concentrating to obtain clear paste with the relative density of 1.22(40 ℃);
(3) adding ethanol into the fluid extract to make ethanol content reach 65% (volume fraction), refrigerating for 48h, filtering, collecting filtrate, recovering ethanol from filtrate until filtrate has no alcohol smell, concentrating the filtrate to fluid extract with relative density of 1.20(40 deg.C), adding ethanol to make ethanol content reach 85% (volume fraction), refrigerating for 24h, filtering, collecting filtrate, adding 40% sodium hydroxide solution to adjust pH of the filtrate to 8.5, refrigerating for 12h, filtering, recovering ethanol from filtrate until filtrate has no alcohol smell, adding water to 500mL, refrigerating for 36h, filtering, collecting filtrate, adding 20% hydrochloric acid solution to adjust pH of the filtrate to 2.0-3.0, heating to 100 deg.C, maintaining for 1h, cooling to room temperature, refrigerating for 24h, filtering, collecting filtrate, adding 1g active carbon into the filtrate, boiling for 30min, cooling to 80 deg.C, filtering, collecting the filtrate, refrigerating for 24h, filtering again, and collecting the filtrate;
(4) and (3) carrying out ultrafiltration treatment on the double distillate obtained in the step (1) and the filtrate finally obtained in the step (3), mixing, adding 5mL of polysorbate 80, adding 7g of sodium chloride, stirring for dissolving, adjusting the pH to 7.6 by using a sodium hydroxide solution with the mass fraction of 20%, adding water for injection to 1000mL, filtering, filling and sealing, and sterilizing to obtain the injection.
Example 6
The preparation method of the wild chrysanthemum injection comprises the following steps:
(1) soaking 1kg of wild chrysanthemum in 10kg of water, distilling with steam, and collecting a primary distillation liquid 1000mL and a distillation residue; redistilling the obtained primary distillate to obtain 500mL of redistillate;
(2) filtering the distillation residue obtained in the step (a) to obtain decoction and solid dregs, adding 6kg of water into the dregs, decocting for 2 times, each time for 1h, filtering, combining the filtrate and the decoction, and concentrating to obtain clear paste with the relative density of 1.22(40 ℃);
(3) adding ethanol into the fluid extract to make ethanol content reach 65% (volume fraction), refrigerating for 48h, filtering, collecting filtrate, recovering ethanol from filtrate until filtrate has no alcohol smell, concentrating the filtrate to fluid extract with relative density of 1.20(40 deg.C), adding ethanol to make ethanol content reach 85% (volume fraction), refrigerating for 24h, filtering, collecting filtrate, adding 40% sodium hydroxide solution to adjust pH of the filtrate to 8.5, refrigerating for 12h, filtering, recovering ethanol from the filtrate until filtrate has no alcohol smell, adding water to 500mL, refrigerating for 36h, filtering, collecting filtrate, adding 20% hydrochloric acid solution to adjust pH of the filtrate to 2.0-3.0, heating to 115 deg.C, maintaining for 1h, cooling to room temperature, refrigerating for 24h, filtering, collecting filtrate, adding 1g active carbon into the filtrate, boiling for 30min, cooling to 80 deg.C, filtering, collecting the filtrate, refrigerating for 24h, filtering again, and collecting the filtrate;
(4) and (3) carrying out ultrafiltration treatment on the double distillate obtained in the step (1) and the filtrate finally obtained in the step (3), mixing, adding 5mL of polysorbate 80, adding 7g of sodium chloride, stirring for dissolving, adjusting the pH to 7.6 by using a sodium hydroxide solution with the mass fraction of 20%, adding water for injection to 1000mL, filtering, filling and sealing, and sterilizing to obtain the injection.
Comparative example 1
The wild chrysanthemum injection is prepared by referring to the preparation method in the current wild chrysanthemum injection standard.
Comparative example 2
The preparation method of comparative example 2 was:
soaking 1000g of wild chrysanthemum in water for 1h, distilling with steam, collecting 1000mL of primary distillate, redistilling, collecting 500mL of secondary distillate, adding 5mL of polysorbate 80 to dissolve the volatile oil, and filtering to obtain filtrate for later use; collecting decoction in the residue, filtering, decocting the residue with water twice, each for 1 hr, filtering, mixing filtrates, concentrating to obtain fluid extract with relative density of 1.22(40 deg.C), adding ethanol to make ethanol content 65%, refrigerating for 48 hr, filtering, recovering ethanol from filtrate until ethanol smell disappears, concentrating to obtain fluid extract with relative density of 1.20(40 deg.C), adding ethanol to make ethanol content 85%, refrigerating for 24 hr, filtering, recovering ethanol from filtrate until ethanol smell disappears, adding water to 500mL, adjusting pH to 4.0-5.0, heating at 90 deg.C for 1 hr, cooling to room temperature, refrigerating for 24 hr, filtering, heating filtrate at 90 deg.C for 1 hr, cooling to room temperature, refrigerating for 24 hr, filtering, adding 1g active carbon into filtrate, boiling for 30min, cooling, filtering, adding heavy distillate into filtrate, mixing, adding 7g sodium chloride, stirring for dissolving, adjusting pH to 6.8 with 20% sodium hydroxide solution, adding water for injection to 1000mL, filtering, bottling, and sterilizing.
Comparative example 3
The preparation method of comparative example 3 was:
soaking 1000g of wild chrysanthemum in water for 1h, distilling with steam, collecting 1000mL of primary distilled liquid, redistilling, and collecting 500mL of secondary distilled liquid for later use; collecting decoction in the residue, filtering, decocting the residue with water twice, each for 1 hr, filtering, mixing filtrates, concentrating to obtain fluid extract with relative density of 1.22(40 deg.C), adding ethanol to make ethanol content 65%, refrigerating for 48 hr, filtering, recovering ethanol from filtrate until ethanol smell disappears, concentrating to obtain fluid extract with relative density of 1.20(40 deg.C), adding ethanol to make ethanol content 85%, refrigerating for 24 hr, filtering, recovering ethanol from filtrate until ethanol smell disappears, adding water to 500mL, refrigerating for 48 hr, filtering, collecting filtrate, adding sodium hydroxide solution into filtrate to adjust pH to 8.0, heating and boiling for 30min, cooling to room temperature, refrigerating for 72 hr, centrifuging supernatant, and filtering with microporous membrane to obtain extractive solution;
adding 5mL of polysorbate 80 into the extract, adding 7g of sodium chloride, stirring for dissolving, adjusting pH to 7.6, adding water for injection to 1000mL, filtering, bottling, and sterilizing.
Experimental example 1
In order to comparatively illustrate the properties of the wild chrysanthemum injection prepared by the methods of the examples and comparative examples of the present invention, the following experiment was performed.
TABLE 1 content of chlorogenic acid in flos Chrysanthemi Indici injection obtained by different treatments
Numbering | Chlorogenic acid content (μ g/mL) |
Example 1 | 53.83 |
Example 2 | 52.78 |
Example 3 | 53.68 |
Example 4 | 48.66 |
Example 5 | 54.54 |
Example 6 | 50.12 |
Comparative example 1 | 40.54 |
Comparative example 2 | 45.25 |
Comparative example 3 | 38.46 |
According to the current standard, the wild chrysanthemum injection should meet the visual foreign matter examination before use, i.e. insoluble substances (the particle size or the length is usually not more than 50 μm) which can be observed under specified conditions by eyes are not needed, and if the turbid, precipitation and the like of the liquid medicine are found, the wild chrysanthemum injection cannot be used. In order to further illustrate the stability and clarity of the wild chrysanthemum injection prepared by the methods of the embodiments and the comparative examples, 400 wild chrysanthemum injections with qualified visible foreign matters are respectively taken and placed at 40 ℃ for 6 months under acceleration and 25 ℃ for 18 months, a lamp inspection method is adopted to inspect the visible foreign matters of the wild chrysanthemum injections, the test method refers to the standard WS-11041(ZD-1041) -2002 and the inspection method of the visible foreign matters in pharmacopoeia of the people's republic of China, the method is to take 400 samples (specification 10ml) to be tested to inspect the visible foreign matters in a lamp inspection box with the illumination of 2000-3000 lx, and the test results are shown in the following table.
TABLE 2 ratio of visible foreign matters in flos Chrysanthemi Indici injection obtained by different treatments
In order to further illustrate the stability of the wild chrysanthemum injection prepared by the methods of the embodiments and the comparative examples, the wild chrysanthemum injection prepared by the embodiments and the comparative examples is taken out and tested under the conditions of 40 ℃ and 75% humidity for 0 month, 3 months and 6 months, and the content of chlorogenic acid is tested, and the test results are shown in table 3.
TABLE 3 accelerated test results of wild chrysanthemum injection obtained by different treatments
Experimental example 2
The sample yields of the preparation methods of the examples and comparative examples of the present invention were measured, and the results are shown in table 4.
TABLE 4 qualification rate of flos Chrysanthemi Indici injection obtained by different treatments
Numbering | Percent pass (%) |
Example 1 | 99.3 |
Example 2 | 95.2 |
Example 3 | 98.1 |
Example 4 | 98.9 |
Example 5 | 95.8 |
Example 6 | 98.4 |
Comparative example 1 | 80.2 |
Comparative example 2 | 91.4 |
Comparative example 3 | 83.8 |
Finally, it should be noted that: the above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.
Claims (19)
1. The preparation method of the wild chrysanthemum injection is characterized by comprising the following steps:
(a) distilling flos Chrysanthemi Indici with water to obtain distillate and distillation residue; redistilling the distillate to obtain redistillate, refrigerating, and filtering;
(b) filtering the distillation residue in the step (a) to obtain a decoction and solid dregs, decocting the dregs in water for 1-2 times, filtering, combining the filtrate with the decoction, and concentrating to obtain a clear paste;
(c) performing secondary alcohol precipitation treatment on the clear paste, collecting filtrate, adjusting the pH of the filtrate to 7.0-8.5, refrigerating, filtering, collecting filtrate, and removing ethanol until the filtrate has no alcohol smell; adding water to make 1mL solution contain 1.0-2.0g crude drug, cooling, filtering, adjusting pH of the filtrate to 2-5, heating to 100-;
(d) ultrafiltering the filtrates obtained in the steps (a) and (c), mixing, adding polysorbate 80 and an isoosmotic adjusting agent, adjusting pH to 7.0-8.5, adding water to a specified amount, and filtering to obtain the final product;
in the step (d), the molecular weight cut-off is 5KD-50KD in the ultrafiltration treatment.
2. The method for preparing wild chrysanthemum injection according to claim 1, wherein in the step (c), the second alcohol precipitation treatment comprises: adding ethanol into the fluid extract to make ethanol content reach 60-85%, refrigerating, filtering, concentrating the filtrate to obtain fluid extract, adding ethanol to make ethanol content reach 60-85%, refrigerating, and filtering.
3. The preparation method of wild chrysanthemum injection according to claim 1, wherein in the step (c), the clear paste is subjected to secondary alcohol precipitation treatment, filtrate is collected, and the pH of the filtrate is adjusted to 8.0-8.5.
4. The preparation method of wild chrysanthemum injection according to claim 1, wherein in the step (c), the clear paste is subjected to secondary alcohol precipitation treatment, filtrate is collected, and the pH of the filtrate is adjusted to 8.5.
5. The method as claimed in claim 1, wherein in step (c), the pH of the filtrate is adjusted to 2-5, heated to 100-115 ℃ and kept for 0.5-1.5h, then refrigerated and filtered.
6. The method for preparing the wild chrysanthemum injection as claimed in claim 5, wherein the pH of the filtrate is adjusted to 2-5 and heated to 110-115 ℃.
7. The method for preparing wild chrysanthemum injection according to claim 6, wherein the pH of the filtrate is adjusted to 2-5, heated to 110 ℃ and kept for 1 h.
8. The method for preparing wild chrysanthemum injection according to claim 1, wherein in the step (c), the pH of the filtrate is adjusted to 2-5 by hydrochloric acid solution.
9. The method for preparing wild chrysanthemum injection according to claim 8, wherein the mass fraction of the hydrochloric acid solution is 15-25%.
10. The method for preparing the wild chrysanthemum injection according to claim 1, wherein the molecular weight cut-off in the ultrafiltration treatment in the step (d) is 10 KD.
11. The method for preparing wild chrysanthemum injection according to claim 1, wherein the adsorbent is activated carbon.
12. The method for preparing wild chrysanthemum injection according to claim 11, wherein the amount of the added active carbon is 0.1-0.5g/100 mL.
13. The method for preparing wild chrysanthemum injection according to claim 11, wherein the amount of the added active carbon is 0.3g/100 mL.
14. The method for preparing wild chrysanthemum injection according to claim 1, wherein in the step (c), the adsorbent is added and then heated to 80-100 ℃ for 30-60 min.
15. The method for preparing wild chrysanthemum injection according to claim 14, wherein in the step (c), the temperature is raised to 100 ℃ and maintained for 30min after the addition of the adsorbent.
16. The method for preparing wild chrysanthemum injection according to claim 1, wherein in the step (c), the adsorbent is added, and then the mixture is heated to 80-100 ℃ and filtered at 60-80 ℃.
17. The method for preparing wild chrysanthemum injection according to claim 16, wherein in step (c), the adsorbent is added, and then the mixture is heated to 100 ℃ and filtered at 80 ℃.
18. The method according to claim 1, wherein the water is added to a predetermined amount in step (d), and the mixture is filtered, filled, and sterilized.
19. The wild chrysanthemum injection prepared by the preparation method of the wild chrysanthemum injection of any one of claims 1 to 18.
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CN105106270A (en) * | 2015-10-10 | 2015-12-02 | 江西天施康中药股份有限公司 | Preparation method for mother chrysanthemum injection |
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CN105106270A (en) * | 2015-10-10 | 2015-12-02 | 江西天施康中药股份有限公司 | Preparation method for mother chrysanthemum injection |
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