CN114931565A - Preparation method of quassia atomization inhalation solution - Google Patents
Preparation method of quassia atomization inhalation solution Download PDFInfo
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- CN114931565A CN114931565A CN202210348261.7A CN202210348261A CN114931565A CN 114931565 A CN114931565 A CN 114931565A CN 202210348261 A CN202210348261 A CN 202210348261A CN 114931565 A CN114931565 A CN 114931565A
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- 229940013788 quassia Drugs 0.000 title claims abstract description 115
- 229940041682 inhalant solution Drugs 0.000 title claims abstract description 55
- 238000000889 atomisation Methods 0.000 title claims abstract description 48
- 238000002360 preparation method Methods 0.000 title claims abstract description 34
- 240000003085 Quassia amara Species 0.000 title 1
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- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
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- A61K9/12—Aerosols; Foams
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
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Abstract
The invention provides a preparation method of quassia atomization inhalation solution, which is characterized in that the quassia atomization inhalation solution comprises quassia extract, an osmotic pressure regulator, a surfactant, a pH regulator and water for injection. The quassia atomization inhalation solution is directly inhaled into a respiratory system in an atomization mode through an atomizer, acts on focuses such as bronchus, lung and the like, is fast to absorb and act quickly, improves the concentration of respiratory tract medicines, reduces the administration dosage, reduces the distribution of the medicines in other tissues, reduces the side effects of the medicines, and realizes low-dose, quick and effective treatment.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to a preparation method of quassia atomization inhalation solution.
Background
The ramulus Et folium Picrasmae is dry branch and leaf of ramulus Et folium Picrasmae of Simaroubaceae, has effects of clearing away heat and toxic materials, and relieving inflammation, and can be used for treating wind-heat type common cold, sore throat, diarrhea, dysentery, eczema, skin sore, furuncle, and venomous snake bite. Pharmacological and clinical researches on quassia quassioides by the pharmaceutical research institute of the academy of Chinese medical sciences in the last 70 th century show that various preparations of quassia quassioides have good curative effects on various inflammations of the respiratory system, the digestive system and the urinary system. At present, the quassia preparation is marketed into two preparation types, namely tablets and injections, and the oral tablets are mainly used for treating bacillary dysentery, acute enteritis and various acute infectious diseases; the quassia injection is used for treating common cold, upper respiratory infection, acute tonsillitis, enteritis, bacillary dysentery, etc.
Chinese patent application CN200510055291.5 discloses a method for preparing quassia injection, which comprises extracting with alkaline ethanol and precipitating with acid to obtain effective components from quassia. However, in the application of respiratory system disease treatment, the quassia injection mostly adopts intramuscular injection, which is an invasive treatment means, and the quassia injection has slow speed and poor drug absorption through tissue absorption and is easy to cause local tissue infection. This method of administration significantly limits its use in the treatment of respiratory diseases.
The aerosol inhalation therapy is a green administration way, can directly transmit the medicament to respiratory tract, acts on focuses of bronchus, lung and the like, has quick absorption and quick action, improves the medicament concentration of the respiratory tract, reduces the administration dosage, reduces the distribution of the medicament in other tissues, reduces the side effect of the medicament, realizes the quick and effective treatment with low dosage, and provides an important administration way for children patients who are inconvenient to administer by oral administration and blood vessels. The clinical observation of the quassia injection aerosol inhalation for treating the acute upper respiratory tract infection of children (119-120 nd 22 nd volume 32 of 2016 of doctors in China) reports that the quassia injection aerosol inhalation for treating the acute upper respiratory tract infection of children has remarkable clinical effect. However, the quassia injection as an aerosol inhalation solution for clinical treatment exceeds the use method specified in the specification, certain potential safety hazards exist, and in order to improve the clinical medication safety, a safe and effective dosage form specially aiming at the aerosol inhalation treatment is urgently needed to be developed.
Disclosure of Invention
Therefore, in order to solve the potential safety hazard that the quassia injection is directly used in the aerosol inhalation treatment, the invention provides a preparation method of quassia aerosol inhalation solution, the formulation of the quassia aerosol inhalation solution has safe components, good stability and convenient storage, and most of particles generated after the aerosol inhalation are smaller than 5 microns, which is beneficial to the deposition of the medicament in trachea, bronchus and bronchiole.
The invention is implemented by the following technical scheme:
the preparation method of the quassia atomization inhalation solution is characterized in that the quassia atomization inhalation solution comprises the components of quassia extract, an osmotic pressure regulator, a surfactant, a pH regulator and water for injection;
wherein the quassia atomization inhalation solution comprises the following preparation steps:
step (1): preparing a quassia extract by a quassia extraction device for later use;
step (2): adding the quassia extract prepared in the step (1) into a quassia atomization solution preparation device, adding 60-80% of injection water, stirring for dissolving, adjusting the pH of the dissolved solution to 1.0-2.0 by using hydrochloric acid, heating for boiling, cooling to 25-35 ℃, adjusting the pH of the cooled solution to 6.5-7.0 by using a sodium hydroxide solution, and obtaining a solution A for later use;
and (3): adding a surfactant and an osmotic pressure regulator into the solution A obtained in the step (2), stirring for dissolving, and supplementing the water for injection into the dissolved solution to full volume to obtain a solution B for later use;
and (4): adding medical carbon into the solution B obtained in the step (3), stirring for 30min, primarily filtering the stirred solution, then performing ultrafiltration, collecting filtrate, and adjusting the pH of the filtrate to 7.0-7.5 by using a pH regulator to obtain a solution C for later use;
and (5): and (4) subpackaging and sterilizing the solution C obtained in the step (4) to obtain the quassia atomization inhalation solution.
Further, the preparation method of the quassia extract in the step (1) comprises the following specific steps:
a step (101): pulverizing cleaned and dried ramulus Et folium Picrasmae into powder with a pulverizer to obtain raw material powder;
a step (102): adding the raw material powder in the step (101) into a quassia tree extraction device, heating and refluxing the raw material powder by using 80% ethanol in an amount which is 5 times that of the raw material powder, extracting for 2 times, 3 hours each time, combining extracting solutions, transferring the extracting solution to the quassia tree extraction device, concentrating, recovering ethanol, and concentrating into a paste A for later use;
step (103): dissolving the paste A in the step (102) with 10 times of 80% ethanol, adjusting the pH to 9-10 with a sodium hydroxide solution, filtering, transferring the filtrate to a quassia extraction device, concentrating, recovering ethanol, and concentrating into a paste B for later use;
a step (104): and (3) completely dissolving the paste B in the step (103) by using a hydrochloric acid solution with the pH value of 3, standing, filtering, adjusting the pH of the filtrate to 7 by using a sodium hydroxide solution, transferring to a quassia extraction device, concentrating to obtain a paste C, and checking the drying weight loss of the paste C to obtain the quassia extract.
Further, in the step (2), the quassia is atomized and inhaled into the solution, and the content of the quassia extract is 5.00-10.00 g/L; the water for injection is distilled water or water obtained by distilling deionized water.
Further, the surfactant in the step (3) is one or more of tween 80, tween 60 and span 80, and the content depends on the kind of the surfactant, and is usually 1 to 15g/L, preferably 5 to 10 g/L;
the osmotic pressure regulator is one or more of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium bicarbonate, sodium carbonate, glucose and xylitol, the content depends on the type of the osmotic pressure regulator, and is usually 1-15 g/L, preferably 5-10 g/L.
Further, in the step (4), the primary filtration is carried out by using a 0.45 μm microporous filter membrane;
the ultrafiltration can be polysulfone membrane, polysulfone amide membrane or polyacrylonitrile membrane with molecular weight cutoff of 1000;
the pH regulator is inorganic acid or inorganic base, preferably hydrochloric acid or sodium hydroxide.
Further, in the step (5), the subpackaging is carried out in ampoule bottles with the specification of 2mL each;
the sterilization is carried out in a high-pressure steam mode, and the temperature of the steam sterilization is 115-121 ℃; the steam sterilization time is 15-30 min.
Further, the quassia extraction device in step (1) includes: an extraction and concentration tank and an ethanol recovery tank.
The top of the extraction and concentration tank is provided with a vacuum pump and an exhaust hole, a first condensing device is arranged above the extraction and concentration tank, the side wall of the extraction and concentration tank is provided with a feed inlet, a pH display and a temperature display, and the bottom of the extraction and concentration tank is provided with a heating layer and a discharge hole; a second condensing device is arranged above the ethanol recovery tank, and a liquid outlet is formed in the side wall of the ethanol recovery tank; the ethanol recovery tank is communicated with the extraction and concentration tank through a first pipeline and a second pipeline, and the first pipeline and the second pipeline are respectively provided with a first valve and a second valve.
Further, the quassia atomization solution preparation device in the step (2) comprises: a stirring tank and a liquid storage tank;
the stirring tank is characterized in that a feed inlet, a tank body, a first pH displayer and a temperature displayer are arranged at the top of the stirring tank, a supporting plate is arranged on the side edge of the tank body, a first motor is arranged on the supporting plate, one end of a first rotating shaft is connected with the first motor, the other end of the first rotating shaft is connected with the inside of a first bearing seat, the first bearing seat is fixed at the bottom of the tank body, a first gear is fixed on the first rotating shaft, the first gear is meshed with a second gear, the second gear is fixed on a threaded rod, the threaded rod is connected with a second bearing seat, the second bearing seat is connected and fixed at the bottom of the tank body, a connecting rod is arranged on the threaded rod, a second motor is arranged at the top of the tank body, the second motor is connected with a second rotating shaft, the other end of the second rotating shaft is connected with a third bearing seat, a lug is arranged on the second rotating shaft, the second rotating shaft is connected with a first friction wheel through the lug, a sliding sleeve is arranged on the second rotating shaft, the sliding sleeve is arranged below the first friction wheel, one end of the connecting rod is fixed on the sliding sleeve, the first friction wheel is contacted with the second friction wheel, the third rotating shaft is connected with the second friction wheel, a third gear is arranged on the third rotating shaft, the third gear is meshed with a fourth gear, the fourth gear is connected with a fourth rotating shaft, a stirring paddle is arranged on the fourth rotating shaft, rubber stop blocks are arranged at two ends of the stirring paddle, a sliding block is arranged on the stirring paddle, one end of the sliding block is connected with a spring, the other end of the spring is fixed at the joint of the stirring paddle and the fourth rotating shaft, a first hinge is arranged on the sliding block, a second hinge is arranged on the fourth rotating shaft, a stirring rod is connected with the third hinge through the first hinge, the second hinge and the second hinge, a heating layer is arranged at the bottom of the stirring tank, a slag discharge port is arranged at one side of the stirring tank, a baffle is arranged at the other side of the stirring tank, a sliding block is arranged on the baffle, and the sliding block is driven by a second motor to enable the baffle to move up and down;
the top of the liquid storage tank is provided with a second pH display, a vacuum pump and an exhaust hole, one side of the liquid storage tank is provided with a liquid discharge port, the other side of the liquid storage tank is connected with the stirring tank through a baffle, when the baffle is opened upwards, the stirring tank is communicated with the liquid storage tank, a filter plate is arranged in the position, close to the baffle, of the liquid storage tank, a primary filter membrane is arranged on the surface of the filter plate, close to one side of the baffle, and an ultrafiltration membrane is arranged on the other side of the filter plate.
Further, the quassia atomization inhalation solution is directly inhaled into a respiratory system in an atomization mode through an atomizer.
Furthermore, the quassia atomization inhalation solution can be used for treating upper respiratory tract infection and other diseases related to respiratory infection.
Further, the RBF-PID algorithm for extracting the temperature of the concentration tank is as follows:
u(t)＝u(t-1)+K P (t)+K I (t)+K D (t)
and adjusting PID parameters through an RBF neural network, wherein an RBF training objective function is as follows:
obtaining PID control parameters:
wherein: u (t) is the control quantity of temperature output, e (t) is the temperature error of the extraction and concentration tank, mu is the learning rate, K P (t-1)、K I (t-1)、K D (t-1) are PID parameters at the sampling time t-1,
the output sensitivity of the temperature control.
The invention has the beneficial effects that:
(1) the quassia atomization inhalation solution solves the problem of potential safety hazard existing in the process of directly using quassia injection as the atomization inhalation solution for clinical treatment.
(2) The formula of the quassia atomization inhalation solution is safe in components, and the content of total alkaloids reaches the standard of quassia injection; the accelerated stability investigation test of the product discovers that the quassia atomization inhalation solution has good stability and is convenient to store; in addition, in-vitro atomization performance tests show that the quassia atomization inhalation solution has good atomization performance, most of particles generated after atomization have the particle size smaller than 5 microns, so that the quassia atomization inhalation solution is beneficial to medicine deposition on trachea, bronchus and bronchiole, and can exert ideal clinical curative effect.
(3) According to the preparation method of the quassia atomization inhalation solution, the whole extraction process can be completed in the extraction concentration tank, the operation is simple and convenient, the recycled ethanol is convenient to be reused, the production cost is reduced, the temperature difference between the temperature in the extraction concentration tank and the preset temperature can be controlled within 0.7 ℃ by adopting the RBF-PID algorithm, the accurate control of the temperature of the extraction concentration tank is realized, and the reflux extraction and concentration processes of the quassia are facilitated; in the liquid device is joined in marriage to quassia atomized solution, make the slider slide on the stirring rake through changing stirring speed, the angle that drives between the puddler changes, forms the shearing of different angles to liquid, makes the stirring more even, has increased the ultrafiltration simultaneously and has filtered, has controlled macromolecular substance's residue, has reduced the adverse reaction that arouses by macromolecular substance.
Drawings
FIG. 1 is a schematic view of the structure of the quassia tree extraction device of the present invention;
FIG. 2 is a schematic structural view of a quassia atomization solution preparation device of the present invention;
fig. 3 is a schematic structural diagram of the box body in fig. 2.
Wherein, 101-an extraction concentration tank, 102-an ethanol recovery tank, 103-a feed inlet, 104-a pH display, 105-a temperature display, 106-a heating layer, 107-a discharge outlet, 108-a first condensing device, 109-an exhaust hole, 110-a vacuum pump, 111-a first pipeline, 112-a first valve, 113-a second condensing device, 114-a liquid discharge outlet, 115-a second valve and 116-a second pipeline; 201-a stirring tank, 202-a liquid storage tank, 203-a feed inlet, 204-a first motor, 205-a fourth rotating shaft, 206-a stirring paddle, 207-a heating layer, 208-a slag discharge port, 209-a first pH display, 210-a temperature display, 211-a second motor, 212-a sliding block, 213-a baffle, 214-a filter plate, 215-an ultrafiltration membrane, 216-a primary filter membrane, 217-a second pH display, 218-a vacuum pump, 219-an exhaust hole, 220-a liquid discharge port, 221-a rubber block, 222-a stirring rod, 223-a third hinge, 224-a spring, 225-a first hinge, 226-a second hinge, 227-a sliding block, 228-a second motor, 229-a box body, 230-a supporting plate and 231-a first rotating shaft, 232-first gear, 233-second gear, 234-connecting rod, 235-threaded rod, 236-second rotating shaft, 237-third gear, 238-fourth gear, 239-first bearing seat, 240-second bearing seat, 241-third bearing seat, 242-first friction wheel, 243-second friction wheel, 244-third rotating shaft, 245-sliding sleeve.
Detailed Description
The invention is further illustrated by the following examples, including but not limited to the following examples.
The quassia extracts used in the following examples were prepared by the laboratory.
Example 1
The preparation method of the quassia extract comprises the following steps:
(1) crushing 5000g of cleaned and dried picrasma quassioides into powder by using a crusher, putting the powder into a picrasma quassioides extraction device, performing heating reflux extraction by using 80% ethanol in an amount which is 5 times that of the powder, extracting for 2 times, each time for 3 hours, combining extracting solutions, transferring the extracting solution to the picrasma quassioides extraction device, concentrating, recovering ethanol, and concentrating into a paste A for later use;
(2) dissolving the paste A with 10 times of 80% ethanol, adjusting pH to 9 with sodium hydroxide solution, filtering, transferring the filtrate to ramulus Et folium Picrasmae extraction device, concentrating, recovering ethanol, and concentrating to obtain paste B;
(3) and completely dissolving the paste B by using a hydrochloric acid solution with the pH value of 3, standing, filtering, adjusting the pH of the filtrate to 7 by using a sodium hydroxide solution, transferring to a quassia extraction device, concentrating into a paste C, and checking the drying weight loss of the paste C to obtain the quassia extract.
In example 1, the RBF-PID algorithm for extracting the temperature of the concentration tank is as follows:
u(t)＝u(t-1)+K P (t)+K I (t)+K D (t)
and adjusting PID parameters through an RBF neural network, wherein an RBF training objective function is as follows:
and obtaining PID control parameters:
wherein: u (t) is the control quantity of temperature output, e (t) is the temperature error of the extraction and concentration tank, mu is the learning rate, K P (t-1)、K I (t-1)、K D (t-1) are PID parameters at the sampling time t-1,
is the output sensitivity of the temperature control.
The beneficial technical effects of the technical scheme are as follows: the RBF-PID algorithm can control the temperature difference between the temperature in the extraction and concentration tank and the preset temperature within 0.7 ℃, so that the temperature of the extraction and concentration tank can be accurately controlled, and the backflow extraction and concentration process of the quassia is facilitated.
Example 2
The preparation formula of the invention is as follows:
the preparation method comprises the following steps:
(1) adding ramulus Et folium Picrasmae extract into ramulus Et folium Picrasmae atomized solution preparation device, adding 60% injectable water, stirring to dissolve, adjusting pH of the dissolved solution to 1.0 with hydrochloric acid, heating to boil, cooling to 35 deg.C, adjusting pH of the cooled solution to 7.0 with sodium hydroxide solution to obtain solution A;
(2) adding sodium chloride and tween 80 into the solution A, stirring for dissolving, and adding water for injection into the dissolved solution to full volume to obtain a solution B;
(3) adding a proper amount of medicinal carbon into the solution B, stirring for 30min, filtering the stirred solution by using a 0.45-micron microporous filter membrane, then filtering by using a polysulfone membrane with the molecular weight of 1000, collecting filtrate, and adjusting the pH value to 7.0 by using sodium hydroxide to obtain a solution C;
(4) and (3) filling 2mL of the solution C into ampoule bottles, sterilizing by adopting high-pressure steam, and sterilizing at 121 ℃ for 15min to obtain the quassia atomization inhalation solution.
Example 3
The prescription of the preparation of the invention is as follows:
the preparation method comprises the following steps:
(1) adding ramulus Et folium Picrasmae extract into ramulus Et folium Picrasmae atomized solution preparation device, adding 80% injectable water, stirring to dissolve, adjusting pH of the dissolved solution to 2.0 with hydrochloric acid, heating to boil, cooling to 30 deg.C, adjusting pH of the cooled solution to 7.5 with sodium hydroxide solution to obtain solution A;
(2) adding potassium chloride and tween 60 into the solution A, stirring for dissolving, and adding water for injection into the dissolved solution to full volume to obtain a solution B;
(3) adding a proper amount of medicinal carbon into the solution B, stirring for 30min, filtering the stirred solution by using a 0.45-micrometer microporous filter membrane, then filtering by using a polysulfone membrane with the molecular weight of 1000, collecting filtrate, and adjusting the pH value to 7.5 by using sodium hydroxide to obtain a solution C;
(4) and (3) filling 2mL of the solution C into ampoule bottles, sterilizing by adopting high-pressure steam at 115 ℃ for 30min to obtain the quassia atomization inhalation solution.
Example 4
The preparation formula of the invention is as follows:
the preparation method comprises the following steps:
(1) adding the quassia extract into a quassia atomization solution preparation device, adding injection water with the preparation amount of 70%, stirring for dissolving, adjusting the pH of the dissolved solution to 1.5 with hydrochloric acid, heating for boiling, cooling to 25 ℃, adjusting the pH of the cooled solution to 7.5 with a sodium hydroxide solution to obtain a solution A;
(2) adding sodium bicarbonate and span 80 into the solution A, stirring for dissolving, and adding injection water into the dissolved solution to full volume to obtain a solution B;
(3) adding a proper amount of medicinal carbon into the solution B, stirring for 30min, filtering the stirred solution by using a 0.45-micrometer microporous filter membrane, then filtering by using a polysulfone membrane with the molecular weight of 1000, collecting filtrate, and adjusting the pH value to 7.5 by using sodium hydroxide to obtain a solution C;
(4) and (3) filling 2mL of the solution C into ampoule bottles, sterilizing by adopting high-pressure steam, and sterilizing at 121 ℃ for 15min to obtain the quassia atomization inhalation solution.
Example 5
The preparation formula of the invention is as follows:
the preparation method comprises the following steps:
(1) adding the quassia extract into a quassia atomization solution preparation device, adding 70% of injection water, stirring for dissolving, adjusting the pH of the dissolved solution to 2.0 by using hydrochloric acid, heating for boiling, cooling to 25 ℃, adjusting the pH of the cooled solution to 7.0 by using a sodium hydroxide solution, and obtaining a solution A;
(2) adding sodium chloride and tween 80 into the solution A, stirring for dissolving, and adding water for injection into the dissolved solution to full volume to obtain a solution B;
(3) adding a proper amount of medicinal carbon into the solution B, stirring for 30min, filtering the stirred solution by using a 0.45-micrometer microporous filter membrane, then filtering by using a polysulfone membrane with the molecular weight of 1000, collecting filtrate, and adjusting the pH value to 7.0 by using sodium hydroxide to obtain a solution C;
(4) and (3) filling 2mL of the solution C into ampoule bottles, sterilizing by adopting high-pressure steam at 115 ℃ for 30min to obtain the quassia atomization inhalation solution.
Comparative example 1
Quassia injection (Jiangxi Qingfeng pharmaceutical Co., Ltd.)
Test example 1: comparison of Total alkaloid content in ramulus Et folium Picrasmae aerosol inhalation solution
The experimental method comprises the following steps: referring to the method for extracting and purifying alkaloid components related to Chinese pharmacopoeia, 20mL of the solutions of the examples 1-4 and the comparative example 1 are precisely sucked into an evaporation dish respectively, the evaporation dish is placed on a water bath and evaporated to dryness, and the residue is dissolved by 10mL of 0.25mol/L sulfuric acid solution, filtered and transferred to a separating funnel. The evaporating dish was washed 2 times with 10mL of 0.05mol/L sulfuric acid solution, filtered, and the filtrates were combined in a separatory funnel. Extracting the solution with 20mL of chloroform for 2 times, collecting and combining chloroform solutions, extracting with 0.25mol/L sulfuric acid solution (10, 10 and 5mL) by shaking for 3 times, discarding chloroform solution, collecting and combining acid solution, adjusting the pH value to about 10 with concentrated ammonia water reagent, quickly extracting with chloroform by shaking for 6 times (20, 15, 10 and 10mL), washing the chloroform extract with 10mL of water for each time, filtering through a filter dish containing anhydrous sodium sulfate, washing the filter dish with 4mL of chloroform for 2 times, combining chloroform solutions, placing the combined chloroform solutions in a dry constant-weight evaporation dish, evaporating on a water bath to dryness, drying at 105 ℃ for 3 hours, quickly and precisely weighing, and calculating to obtain the product. The results are shown in Table 1.
TABLE 1 Total alkaloid content determination
And (4) conclusion: the detection experimental data in table 1 show that the total alkaloid content of the quassia xylocarpa atomization inhalation solvent reaches the standard.
Test example 2: stability testing of quassia aerosol inhalation solutions
The experimental method comprises the following steps: the quassia xylon aerosol inhalation solution prepared in examples 1-4 is placed in a stability test box, is placed for 6 months at 40 +/-2 ℃ and 75% +/-5% relative humidity, accelerated stability investigation of products is carried out, 15 bottles of samples are taken every month, and properties, microorganisms, pH value and total alkaloid content are respectively observed. The results are shown in Table 2.
TABLE 2 stability test results
And (4) conclusion: the experimental results in table 2 show that the properties, microorganisms, pH value and total alkaloid content of the quassia xylocarpa aerosol inhalation solution are not obviously changed compared with 0 month, which indicates that the quassia xylocarpa aerosol inhalation solution obtained by the invention has good stability and is convenient to store.
Test example 3: evaluation of in-vitro atomization performance of quassia atomization inhalation solution
(1) Determination of aerodynamic particle size distribution of quassia spray inhalation solution
The experimental method comprises the following steps: the quassia spray inhalation solution prepared in example 1 was subjected to the method of "chinese pharmacopoeia" 2015 edition, and the sample of example 1 was atomized by a bai atomizer, and the aerodynamic particle size distribution of the quassia spray inhalation solution was measured by NGI (new generation pharmaceutical impactor).
The quassia aerosol inhalation solution prepared in example 1 was tested to have a mass median aerodynamic particle size of 4.527 μm.
And (4) conclusion: the detection result shows that most particles of the atomized and inhaled quassia solution obtained by the invention have the particle size of less than 5 mu m after atomization, can be effectively deposited in trachea, bronchus and bronchiole, and can exert ideal clinical effect.
(2) Quassia aerosol inhalation solution delivery rate and total delivery amount determination
The experimental method comprises the following steps: the operation is carried out according to a method of 'Chinese pharmacopoeia' of 2015 edition, the total alkaloids are used as detection indexes, and a breathing simulator and a Bairui atomizer are adopted to detect the delivery rate and the total delivery amount. Due to the limitation of the method for detecting total alkaloids, 20mL (total alkaloids content is 5.8mg) of quassia atomization inhalation solution prepared in example 1 is adopted for determination in the experiment, and the experimental results are shown in Table 3.
TABLE 3 Total alkaloid based breath simulator test results
And (4) conclusion: the experimental results in table 3 show that the quassia atomization inhalation solution obtained by the invention has better atomization performance.
In one embodiment, as shown in fig. 1, the quassia extraction device comprises: an extraction concentration tank 101 and an ethanol recovery tank 102.
Draw concentrated jar 101 top and be equipped with vacuum pump 110 and exhaust hole 109, draw the interior top of concentrated jar 101 and be equipped with first condensing equipment 108, draw concentrated jar 101 lateral wall and be equipped with feed inlet 103, pH display 104 and temperature display 105, draw concentrated jar 101 bottom and be equipped with zone of heating 106 and bin outlet 107.
A second condensing device 113 is arranged at the upper part in the ethanol recovery tank 102, and a liquid outlet 114 is arranged on the side wall of the ethanol recovery tank 102; the ethanol recovery tank 102 is communicated with the extraction and concentration tank through a first pipeline 111 and a second pipeline 116, and the first pipeline 111 and the second pipeline 116 are respectively provided with a first valve 112 and a second valve 115.
The working principle and the beneficial technical effects of the technical scheme are as follows: pulverizing ramulus Et folium Picrasmae, directly adding into the extraction and concentration tank 101, opening the first condensing unit 108 during extraction, and closing the first valve 112 and the second valve 115; after the extraction is completed, the first condensing device 108 is closed, the vacuum pump 110, the first valve 112 and the second condensing device 113 are opened during concentration, the concentrated ethanol can be directly collected in the ethanol recovery tank 102, and the recovered ethanol can be directly sent to the extraction and concentration tank 101 through the second pipeline 116 by opening the second valve 115. The whole extraction process can be completed in the extraction and concentration tank 101, the operation is simple, the recovered ethanol is convenient for secondary utilization, and the production cost is reduced.
In one embodiment, as shown in fig. 2 to 3, the quassia atomization solution preparation device includes: an agitator tank 201 and a liquid storage tank 202.
The top of the stirring tank 201 is provided with a feed inlet 203, a box body 229, a first pH display 209 and a temperature display 210, the side of the box body 229 is provided with a support plate 230, the support plate 230 is provided with a first motor 204, one end of a first rotating shaft 231 is connected with the first motor 204, the other end of the first rotating shaft is connected with the inside of a first bearing seat 239, the first bearing seat 239 is fixed at the bottom of the box body 229, a first gear 232 is fixed on the first rotating shaft 231, the first gear 232 is meshed with a second gear 233, the second gear 233 is fixed on a threaded rod 235, the threaded rod 235 is connected with a second bearing seat 240, the second bearing seat 240 is connected and fixed at the bottom of the box body 229, the threaded rod 235 is provided with a connecting rod 234, the top of the box body is provided with a second motor 228, the second motor 228 is connected with a second rotating shaft 236, the other end of the second rotating shaft 236 is connected with a third bearing seat 241, the second rotating shaft 236 is provided with a bump, the second rotating shaft 236 is connected with a first friction wheel 242 through the bump, a sliding sleeve 245 is arranged on the second rotating shaft 236, the sliding sleeve 245 is positioned below the first friction wheel 242, one end of the connecting rod 234 is fixed on the sliding sleeve 245, the first friction wheel 242 is in contact with the second friction wheel 243, the third rotating shaft 244 is connected with the second friction wheel 243, the third rotating shaft 244 is provided with a third gear 237, the third gear 237 is meshed with the fourth gear 238, the fourth gear 238 is connected with the fourth rotating shaft 205, the fourth rotating shaft 205 is provided with a stirring paddle 206, two ends of the stirring paddle 206 are provided with rubber stoppers 221, the stirring paddle 206 is provided with a sliding block 227, one end of the sliding block 227 is connected with a spring 224, the other end of the spring 224 is fixed at the joint of the stirring paddle 206 and the fourth rotating shaft 205, the sliding block 227 is provided with a first hinge 225, the fourth rotating shaft 205 is provided with a second hinge 226, the stirring rod 222 is connected with the third hinge 223 through the first hinge 225 and the second hinge 226, the bottom of the stirring tank 201 is provided with a heating layer 207, one side of the stirring tank 201 is provided with a slag discharge port 208, the other side is provided with a baffle 213, the baffle 213 is provided with a slide block 212, and the second motor 211 drives the slide block 212 to enable the baffle 213 to move up and down.
The top of the liquid storage tank 202 is provided with a second pH display 217, a vacuum pump 218 and an exhaust hole 219, one side of the liquid storage tank 202 is provided with a liquid outlet 220, the other side of the liquid storage tank 202 is connected with the stirring tank 201 through a baffle 213, when the baffle 213 is opened upwards, the stirring tank 201 is communicated with the liquid storage tank 202, a filter plate 214 is arranged in the liquid storage tank 202 at a position close to the baffle 213, a primary filter membrane 216 is arranged on the surface of the filter plate 214 at one side close to the baffle 213, and an ultrafiltration membrane 215 is arranged on the other side.
The working principle and the beneficial technical effects of the technical scheme are as follows: adding the cumwood extract and water for injection into a stirring tank, turning on a first motor 204 to drive a first gear 232 on a first rotating shaft 231 to rotate, driving a second gear 233 to rotate, driving a threaded rod 235 to rotate, driving a connecting rod 234 on the threaded rod 235 to move up and down, driving a sliding sleeve 245 to move up and down, turning on a second motor 228 to drive a second rotating shaft 236 to rotate, driving a first friction wheel 242 on the second rotating shaft 236 to rotate, driving a second friction wheel 242 to rotate, driving a third gear 237 on a third rotating shaft 244 to rotate, driving a fourth gear 238 to rotate by the third gear 237, driving the fourth rotating shaft 205 to rotate by the fourth gear 238, changing the rotating speed of the second gear 243 as the first friction wheel 242 slides up and down, changing the stirring speed, sliding a sliding block 227 slides on a stirring paddle 206 to drive the angle between stirring rods 222 to change, and forming different angles of shearing on liquid, the stirring is more uniform. After the quassia extract is dissolved, pH adjusted, boiled, cooled, pH adjusted and volume-fixed decolorized in the stirring tank 201, the second motor 211 is started to drive the sliding block 212 to enable the baffle 213 to slide upwards, the stirring tank 201 is communicated with the liquid storage tank 202, the vacuum pump 218 is started, and the solution passes through the primary filtration membrane 216 and the ultrafiltration membrane 215 to adjust the pH, so that the target solution is obtained. The filtered target solution controls the residue of macromolecular substances and reduces adverse reactions caused by the macromolecular substances.
Finally, it should be noted that: the above-mentioned embodiments only represent some embodiments of the present invention, and are not intended to limit the present invention, and it should be understood that any modifications, equivalent substitutions, improvements, etc. made by those skilled in the art without departing from the spirit of the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (10)
1. The preparation method of the quassia atomization inhalation solution is characterized in that the quassia atomization inhalation solution comprises the components of quassia extract, an osmotic pressure regulator, a surfactant, a pH regulator and water for injection;
wherein the quassia atomization inhalation solution comprises the following preparation steps:
step (1): preparing a quassia extract by a quassia extraction device for later use;
step (2): adding the quassia extract prepared in the step (1) into a quassia atomization solution preparation device, adding 60-80% of injection water, stirring for dissolving, adjusting the pH of the dissolved solution to 1.0-2.0 by using hydrochloric acid, heating for boiling, cooling to 25-35 ℃, adjusting the pH of the cooled solution to 6.5-7.0 by using a sodium hydroxide solution, and obtaining a solution A for later use;
and (3): adding a surfactant and an osmotic pressure regulator into the solution A obtained in the step (2), stirring for dissolving, and supplementing the water for injection to the full amount into the dissolved solution to obtain a solution B for later use;
and (4): adding medical carbon into the solution B obtained in the step (3), stirring for 30min, primarily filtering the stirred solution, then performing ultrafiltration, collecting filtrate, and adjusting the pH of the filtrate to 7.0-7.5 by using a pH regulator to obtain a solution C for later use;
and (5): and (4) subpackaging and sterilizing the solution C obtained in the step (4) to obtain the quassia atomization inhalation solution.
2. The method for preparing quassia spinosa aerosol inhalation solution according to claim 1, wherein the quassia spinosa extract is prepared in step (1) by the following specific steps:
a step (101): pulverizing cleaned and dried ramulus Et folium Picrasmae into powder with a pulverizer to obtain raw material powder;
a step (102): adding the raw material powder in the step (101) into a quassia tree extraction device, heating and refluxing the raw material powder by using 80% ethanol in an amount which is 5 times that of the raw material powder, extracting for 2 times, 3 hours each time, combining extracting solutions, transferring the extracting solution to the quassia tree extraction device, concentrating, recovering ethanol, and concentrating into a paste A for later use;
step (103): dissolving the paste A in the step (102) with 10 times of 80% ethanol, adjusting the pH to 9-10 with a sodium hydroxide solution, filtering, transferring the filtrate to a quassia extraction device, concentrating, recovering ethanol, and concentrating to obtain a paste B for later use;
a step (104): and (3) completely dissolving the paste B in the step (103) by using a hydrochloric acid solution with the pH value of 3, standing, filtering, adjusting the pH of the filtrate to 7 by using a sodium hydroxide solution, transferring to a quassia extraction device, concentrating to obtain a paste C, and checking the drying weight loss of the paste C to obtain the quassia extract.
3. The method for preparing quassia xylocarpa atomization and inhalation solution according to claim 1, wherein in the step (2), the content of the quassia xylocarpa extract in the quassia xylocarpa atomization and inhalation solution is 5.00-10.00 g/L;
the water for injection is distilled water or water obtained by distilling deionized water.
4. The method for preparing quassia spray inhalation solution according to claim 1, wherein in step (3), the surfactant is one or more of tween 80, tween 60 and span 80, the content depends on the kind of surfactant, and is usually 1-15 g/L;
the osmotic pressure regulator is one or more of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium bicarbonate, sodium carbonate, glucose and xylitol, the content depends on the type of the osmotic pressure regulator, and is usually 1-15 g/L.
5. The method for preparing quassia spray inhalation solution according to claim 1, wherein in step (4), the primary filtration is performed with a 0.45 μm microporous membrane;
the ultrafiltration can be polysulfone membrane, polysulfone amide membrane or polyacrylonitrile membrane with molecular weight cutoff of 1000;
the pH regulator is inorganic acid or inorganic base.
6. The method for preparing quassia aerosol inhalation solution according to claim 1, wherein in step (5), the aliquots are filled into ampoules with a size of 2mL each;
the sterilization is carried out in a high-pressure steam mode, and the temperature of the steam sterilization is 115-121 ℃; the steam sterilization time is 15-30 min.
7. The method for preparing quassia xylon aerosol inhalation solution according to claim 1, wherein the quassia xylon extraction device in step (1) comprises: an extraction and concentration tank (101) and an ethanol recovery tank (102);
the top of the extraction and concentration tank (101) is provided with a vacuum pump (110) and an exhaust hole (109), a first condensing device (108) is arranged above the interior of the extraction and concentration tank (101), the side wall of the extraction and concentration tank (101) is provided with a feeding hole (103), a pH display (104) and a temperature display (105), and the bottom of the extraction and concentration tank (101) is provided with a heating layer (106) and a discharge hole (107);
a second condensing device (113) is arranged above the inside of the ethanol recovery tank (102), and a liquid outlet (114) is formed in the side wall of the ethanol recovery tank (102); the ethanol recovery tank (102) is communicated with the extraction and concentration tank through a first pipeline (111) and a second pipeline (116), and the first pipeline (111) and the second pipeline (116) are respectively provided with a first valve (112) and a second valve (115).
8. The method for preparing quassia oleifera atomized inhalation solution according to claim 1, wherein the quassia oleifera atomized inhalation solution preparation device in the step (2) comprises: a stirring tank (201) and a liquid storage tank (202);
the top of the stirring tank (201) is provided with a feed port (203), a tank body (229), a first pH display (209) and a temperature display (210), a support plate (230) is arranged on the side edge of the tank body (229), a first motor (204) is arranged on the support plate (230), one end of a first rotating shaft (231) is connected with the first motor (204), the other end of the first rotating shaft is connected with the inside of a first bearing seat (239), the first bearing seat (239) is fixed at the bottom of the tank body (229), a first gear (232) is fixed on the first rotating shaft (231), the first gear (232) is meshed with a second gear (233), the second gear (233) is fixed on a threaded rod (235), the threaded rod (235) is connected with a second bearing seat (240), the second bearing seat (240) is connected and fixed at the bottom of the tank body (229), a connecting rod (234) is arranged on the threaded rod (235), a second motor (228) is arranged at the top of the tank body (229), the second motor (228) is connected with the second rotating shaft (236), the other end of the second rotating shaft (236) is connected with the third bearing seat (241), a convex block is arranged on the second rotating shaft (236), the second rotating shaft (236) is connected with the first friction wheel (242) through the convex block, a sliding sleeve (245) is arranged on the second rotating shaft (236), the sliding sleeve (245) is positioned below the first friction wheel (242), one end of the connecting rod (234) is fixed on the sliding sleeve (245), the first friction wheel (242) is in contact with the second friction wheel (243), the third rotating shaft (244) is connected with the second friction wheel (243), a third gear (237) is arranged on the third rotating shaft (244), the third gear (237) is meshed with a fourth gear (238), the fourth gear (238) is connected with the fourth rotating shaft (205), a stirring paddle (206) is arranged on the fourth rotating shaft (205), rubber stoppers (221) are arranged at two ends of the stirring paddle (206), and a sliding block (227) is arranged on the stirring paddle (206), one end of a sliding block (227) is connected with a spring (224), the other end of the spring (224) is fixed at the joint of a stirring paddle (206) and a fourth rotating shaft (205), a first hinge (225) is arranged on the sliding block (227), a second hinge (226) is arranged on the fourth rotating shaft (205), a stirring rod (222) is connected with a third hinge (223) through the first hinge (225), a heating layer (207) is arranged at the bottom of the stirring tank (201), a slag discharge port (208) is arranged on one side of the stirring tank (201), a baffle (213) is arranged on the other side of the stirring tank (201), a sliding block (212) is arranged on the baffle (213), and the second motor (211) drives the sliding block (212) to enable the baffle (213) to move up and down;
the top of the liquid storage tank (202) is provided with a second pH display (217), a vacuum pump (218) and an exhaust hole (219), one side of the liquid storage tank (202) is provided with a liquid outlet (220), the other side of the liquid storage tank is connected with the stirring tank (201) through a baffle (213), when the baffle (213) is opened upwards, the stirring tank (201) is communicated with the liquid storage tank (202), a filter plate (214) is arranged in the liquid storage tank (202) close to the baffle (213), a primary filter membrane (216) is arranged on the surface of the filter plate (214) close to one side of the baffle (213), and an ultrafiltration membrane (215) is arranged on the other side of the liquid storage tank.
9. The method for preparing quassia spinosa aerosolized inhalation solution according to claim 1, wherein said quassia spinosa aerosolized inhalation solution is directly inhaled into the respiratory system in an aerosolized form by means of an atomizer.
10. The method for preparing quassia spinosa aerosol inhalation solution according to claim 1, wherein the quassia spinosa aerosol inhalation solution is used for treating upper respiratory tract infection and other respiratory infection-related diseases.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117899164A (en) * | 2024-03-18 | 2024-04-19 | 广州中医药大学(广州中医药研究院) | Novel aerosolized dosage form system and its use in the preparation of a medicament |
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| CN1730014A (en) * | 2005-08-05 | 2006-02-08 | 北京阜康仁生物制药科技有限公司 | Novel drug administration route of semen armeniacae amarum injection, its preparation process and new indications |
| CN101239249A (en) * | 2008-03-06 | 2008-08-13 | 永定采善堂生物质提炼有限公司 | Device for extracting alcohol soluble plant component |
| CN110327821A (en) * | 2019-06-20 | 2019-10-15 | 徐州亚泰电机有限公司 | A kind of petroleum machinery device of suitable thickened oil recovery |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1730014A (en) * | 2005-08-05 | 2006-02-08 | 北京阜康仁生物制药科技有限公司 | Novel drug administration route of semen armeniacae amarum injection, its preparation process and new indications |
| CN101239249A (en) * | 2008-03-06 | 2008-08-13 | 永定采善堂生物质提炼有限公司 | Device for extracting alcohol soluble plant component |
| CN110327821A (en) * | 2019-06-20 | 2019-10-15 | 徐州亚泰电机有限公司 | A kind of petroleum machinery device of suitable thickened oil recovery |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN117899164A (en) * | 2024-03-18 | 2024-04-19 | 广州中医药大学(广州中医药研究院) | Novel aerosolized dosage form system and its use in the preparation of a medicament |
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Application publication date: 20220823 |