CN109512880A - A kind of sucking preparation and preparation method thereof, application - Google Patents
A kind of sucking preparation and preparation method thereof, application Download PDFInfo
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- CN109512880A CN109512880A CN201910031538.1A CN201910031538A CN109512880A CN 109512880 A CN109512880 A CN 109512880A CN 201910031538 A CN201910031538 A CN 201910031538A CN 109512880 A CN109512880 A CN 109512880A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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)
- A61K36/75—Rutaceae (Rue family)
- A61K36/752—Citrus, e.g. lime, orange or lemon
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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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
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- A61K9/007—Pulmonary tract; Aromatherapy
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Abstract
The present invention provides a kind of sucking preparation and preparation method thereof, application.The sucking preparation includes active constituent Exocarpium Citri Grandis extract, the pharmaceutic adjuvant suitable for inhalation；The Exocarpium Citri Grandis extract is the mixture of the extracting solution of Exocarpium Citri Grandis extracting solution, the perhaps mixture for the volatile oil of Exocarpium Citri Grandis and the extracting solution of Exocarpium Citri Grandis or the distillate and Exocarpium Citri Grandis for Exocarpium Citri Grandis；Exocarpium Citri Grandis extract included in sucking preparation described in every 100ml is prepared by 10g~60g Exocarpium Citri Grandis；The pH value of the sucking preparation is adjusted to 4.0~8.5 using pH adjusting agent.The present invention is using Exocarpium Citri Grandis extracting solution and volatile oil or distillate as effective component, and after being included using cyclodextrin to volatile oil or distillate, pH value is adjusted to suitable concentration by cooperation, finally ensures that the atomized inhalation of Exocarpium Citri Grandis is uniform, stablizes.
Description
Technical field
The present invention relates to technical field of medicine, more particularly to a kind of sucking preparation and preparation method thereof, application.
Background technique
Respiratory disease is common disease, frequently-occurring disease, common classical symptom: cough, phlegm, asthma.The atmosphere got worse is dirty
The influence of the factors such as dye, the increase of smoking population, aging of population, the disease incidence of various respiratory diseases, the death rate have increasing
Nothing subtracts.In recent years, haze swept across China's most area, and it endangers self-evident caused by human body, stands in the breach just
It is the respiratory system and cardiovascular field of human body.
Sucking preparation means that drug is dissolved or dispersed in suitable media, is delivered to respiratory tract with steam or aerosol form
Or lung plays the preparation locally or systemically acted on.Compared with conventional oral formulation, the drug for sucking preparation can directly reach suction
Receipts or site of action, it is rapid-action, it can avoid liver first-pass effect, reduce dosage, reduce side effect.With ejection preparation phase
Than patient compliance can be improved, while can reduce or avoid some drugs adverse reaction.In view of sucking preparation treatment advantage,
Sucking preparation for treating is recommended as preventing and treating the first choice of the respiratory diseases such as asthma, Chronic Obstructive Pulmonary Disease to prescription by multinational
Formula.
Currently, sucking preparation include inhalation aerosol, inhalation powder spray, for atomizer liquid preparation and can be transformed into
The preparation of steam.Inhalation solution is belonged to wherein for one kind under Neulized inhalation liquid preparation item, is meant through continuous mist
Change device generation for the solution of sucking aerosol.Compare the sucking preparation of other dosage forms, the advantage of inhalation solution further include: prescription
In be not required to be added propellant；Composition and preparation process are relatively easy；Convenient for drug combination；Deliberately cooperate without patient, just
In children, the elderly, some patients with severe symptoms and other cannot be advantageously used the patient medication of inhalation aerosol and inhalation powder spray.
In addition the development of nebulization equipment in recent years, fog inhalation therapy have become the important of current clinical treatment respiratory disease
Means.But the atomization preparation of country's listing is considerably less, common that non-atomized preparation is acted temporarily as atomization preparation during clinical application
It uses, belongs to super specification medication, there are problems.
Exocarpium Citri Grandis is rutaceae Citrus grandis Citrus grandis ' Tomentosay ' or shaddock Citrus grandis
(L.) the prematurity young fruit of Osbeck or maturescent dry pericarp, property acrid, bitter, warm have regulating the flow of QI to ease the stomach, eliminating dampness and eliminating phlegm function
Effect.For coughing with a lot of sputum, dyspepsia is got sick from drinking too much wine, and evil of vomitting ruffian is bored.Modern research shows that Exocarpium Citri Grandis is rich in flavones, cumarin, polysaccharide, waves
The a variety of active ingredients such as hair oil have significant resolving sputum, the pharmacological actions such as cough-relieving, relieving asthma, is anti-inflammatory.Traditional technology disclosedization tangerine
The oral agents such as oral solution, tablet or capsule are made mainly using Citrus grandis as raw material in red oral preparation and its production method
Type has good relieving cough and reducing sputum effect.But the generally existing dose of conventional oral formulation is big, cannot directly act on disease
Affected part position, work problem slow, that utilization rate is low, and with gastrointestinal side effect.
It would therefore be highly desirable to develop a kind of inhalable aerosol drug of pummelo pee medicinal material.
Summary of the invention
Based on this, the present invention is intended to provide a kind of sucking preparation, especially a kind of atomized inhalation of Exocarpium Citri Grandis.The change tangerine
Red atomized inhalation can be good at dissolution and be dispersed into uniform, stable solution body using Exocarpium Citri Grandis extract as effective component
System, and stable storage and can effectively be atomized.
The purpose of the present invention is what is be achieved through the following technical solutions:
A kind of sucking preparation, the sucking preparation includes active constituent Exocarpium Citri Grandis extract, suitable for inhalation
Pharmaceutic adjuvant；The Exocarpium Citri Grandis extract is the extraction of the extracting solution of Exocarpium Citri Grandis or the volatile oil and Exocarpium Citri Grandis of Exocarpium Citri Grandis
The mixture of the extracting solution of the mixture of liquid or the distillate of Exocarpium Citri Grandis and Exocarpium Citri Grandis；
Exocarpium Citri Grandis extract included in sucking preparation described in every 100ml is prepared by 10g~60g Exocarpium Citri Grandis
It arrives；The pH value of the sucking preparation is adjusted to 4.0~8.5 using pH adjusting agent.
The pH value of the sucking preparation is adjusted to 5.0~7.5 using pH adjusting agent in one of the embodiments,.
Inventors have found that pH value influences Exocarpium Citri Grandis inhalant stability.For this purpose, inventor carries out the pH value of the inhalant
It investigates, screens suitable pH adjustable range.Experiments have shown that 4.0 or more preparation of pH value is uniform clear solution system, to avoid
Cause physiological stimulation, the preparation pH value upper limit is set as 8.5.Subsequent preparation stability investigates discovery Exocarpium Citri Grandis aerosol inhalation solution
PH value is lower than 5.0, will appear micro insoluble matter in long-term storage process, product stability is not good enough；Exocarpium Citri Grandis aerosol inhalation solution
PH value be higher than 7.5 and decline by a big margin in preceding 3 months pH value of storage.Therefore, Exocarpium Citri Grandis aerosol inhalation solution pH value is most
Good range screening is 5.0~7.5.
The pharmaceutic adjuvant includes cyclodextrin in one of the embodiments,.Cyclodextrin such as α-in the present invention
Cyclodextrin and its derivative, beta-cyclodextrin and its derivative, gamma-cyclodextrin and its derivative.
The cyclodextrin is hydroxy propyl-Beta-ring paste that average substitution degree is 2.0~10.0 in one of the embodiments,
Essence.
The cyclodextrin is hydroxy propyl-Beta-ring paste that average substitution degree is 4.0~5.0 in one of the embodiments,
Essence.
Exocarpium Citri Grandis volatile component is also main pharmacodynamics ingredient, but its solubility in aqueous solution is low, and it is volatile not
Stablize.How its water-soluble and stability is increased to guarantee that the uniform of end product quality and stabilization are inventors in preparation prescription
One of the problem of being paid close attention in screening and preparation process research.By a large number of experiments, final choice is solved by inclusion technique.It grinds
To more than 10 water solubility such as alpha-cyclodextrin and its derivative, beta-cyclodextrin and its derivative, gamma-cyclodextrin and its derivative in studying carefully
Cyclodextrin encapsulated material is screened, as a result, it has been found that these cyclodextrin have different degrees of inclusion to Exocarpium Citri Grandis volatile component
It acts on, wherein hydroxypropyl-β-cyclodextrin inclusion rate highest.Further study show that the average substitution degree of hydroxypropyl-β-cyclodextrin
There is larger impact to the stability of inclusion rate and inclusion compound, the hydroxypropyl-β-cyclodextrin that average substitution degree is 2.0~10.0 is to change
Exocarpium Citri Rubrum volatile component has preferable clathration, and the hydroxypropyl-β-cyclodextrin that wherein degree of substitution is 4.0~5.0 not only includes
Rate is high, and obtained inclusion compound is more stable.
The pharmaceutic adjuvant includes osmotic pressure regulator, corrigent, solvent in one of the embodiments,；The pH tune
It saves agent and selects at least one of sodium hydroxide, potassium hydroxide, sodium bicarbonate.
The osmotic pressure regulator selects potassium chloride, sodium chloride, magnesium chloride, calcium chloride, Portugal in one of the embodiments,
At least one of grape sugar, xylitol, mannitol, sorbierite；The corrigent selects lemon extract, orange flavor, orange fragrant
Essence, grape essence, red bayberry essence, Mint Essence, almond flavour, Steviosin, menthol, aspartame, in sodium cyclamate extremely
Few one kind.
In one of the embodiments, the volatile oil of the Exocarpium Citri Grandis, the distillate of Exocarpium Citri Grandis, Exocarpium Citri Grandis extracting solution be
It is prepared via a method which:
(1) Exocarpium Citri Grandis is taken, adding water, perhaps ethanol solution decocts collection volatile oil or distillate, non-volatile/non-distillation mention
Take product；It filters non-volatile/non-distillation and extracts product, obtain extracting solution A, the dregs of a decoction；
(2) dregs of a decoction are taken, water or ethanol solution is added to decoct, filtering obtains extracting solution B；
(3) merge the extracting solution A, the extracting solution B, Exocarpium Citri Grandis extracting solution is made in concentration.
The ethanol solution is the alcohol-water mixed solution of 0~100% (being free of zero) in one of the embodiments,.
The envelope-bulk to weight ratio of the volatile oil and cyclodextrin is 1:(1~10 in one of the embodiments)；The distillation
The envelope-bulk to weight ratio of liquid and cyclodextrin is 100:(1~10).
It is a further object of the present invention to provide a kind of preparation methods of above-mentioned sucking preparation, include the following steps: taking
Pharmaceutic adjuvant, mixing, filtration, encapsulating, sterilizing is added in Exocarpium Citri Rubrum extract；The pH value of the sucking preparation uses pH adjusting agent tune
Wherein to 4.0~8.5, the Exocarpium Citri Grandis extract is the extracting solution of Exocarpium Citri Grandis or the volatile oil and Exocarpium Citri Grandis of Exocarpium Citri Grandis
The mixture of extracting solution or the distillate of Exocarpium Citri Grandis and Exocarpium Citri Grandis extracting solution mixture.
It include in one of the embodiments, cyclodextrin in the pharmaceutic adjuvant, then the preparation method includes following step
It is rapid:
(1) volatile oil of Exocarpium Citri Grandis or the distillate of Exocarpium Citri Grandis are taken, cyclodextrin is added and is included, inclusion liquid is made；
(2) extracting solution for mixing the inclusion liquid, Exocarpium Citri Grandis, is added pharmaceutic adjuvant, mixing, filtration, encapsulating, sterilizing；Institute
The pH value for stating sucking preparation is adjusted to 4.0~8.5 using pH adjusting agent.
The pH value of the sucking preparation is adjusted to 5.0~7.5 with pH adjusting agent in one of the embodiments, the solvent
Select at least one of water for injection, physiological saline, isotonic glucose solution.
It is a further object of the present invention to provide a kind of above-mentioned sucking preparations in treatment flu, influenza, urgency/chronic throat
Inflammation, urgency/chronic bronchitis, urgency/chronic bronchitis, Chronic Obstructive Pulmonary Disease, bronchial asthma, bronchiectasis, pneumonia,
Cough caused by pulmonary emphysema and pulmonary fibrosis, expectoration, the application in asthma.
Compared with prior art, the invention has the following advantages:
The present invention provides a kind of atomized inhalation of Exocarpium Citri Grandis, and the atomized inhalation is with the extract (Exocarpium Citri Grandis of Exocarpium Citri Grandis
Extract is the mixture or Exocarpium Citri Grandis of the extracting solution perhaps extracting solution of the volatile oil and Exocarpium Citri Grandis of Exocarpium Citri Grandis of Exocarpium Citri Grandis
Distillate and Exocarpium Citri Grandis extracting solution mixture) be effective component, pH value is adjusted to suitable concentration by cooperation, finally
Ensure that the atomized inhalation of gained Exocarpium Citri Grandis is uniform, stablize.Especially further the specific of suitable average substitution degree is selected in cooperation
Cyclodextrin includes volatile oil/distillate in effective component, additionally it is possible to atomized inhalation be avoided to wave during storage
Hair property component content significantly reduces.Exocarpium Citri Grandis aerosol inhalation solution of the present invention also has many advantages, such as that atomizing effect is good, and absorptivity is high.
Detailed description of the invention
Fig. 1: the aerodynamic size distribution map of the Exocarpium Citri Grandis aerosol inhalation solution of embodiment 1 in test example 2 of the present invention.
Specific embodiment
It to facilitate the understanding of the present invention, below will be to invention is more fully described.But the present invention can be to be permitted
Mostly different form is realized, however it is not limited to embodiment described herein.On the contrary, purpose of providing these embodiments is makes
It is more thorough and comprehensive to the understanding of the disclosure.
Unless otherwise defined, all technical and scientific terms used herein and belong to technical field of the invention
The normally understood meaning of technical staff is identical.Term as used herein in the specification of the present invention is intended merely to description tool
The purpose of the embodiment of body, it is not intended that in the limitation present invention.Term as used herein "and/or" includes one or more phases
Any and all combinations of the listed item of pass.
Embodiment 1
It is specific as follows the present embodiment provides a kind of Exocarpium Citri Grandis atomized inhalation and preparation method thereof:
(1) Exocarpium Citri Grandis 200g is taken, 8 times of amount water are added, heating decocts 2 hours, and collects volatile oil, non-volatile extraction product,
Non-volatile extraction product is filtered, extracting solution A, the dregs of a decoction are obtained；
(2) dregs of a decoction add 6 times of amount water again, and heating decocts 2 hours, and filtering obtains extracting solution B；
(3) extracting solution A, extracting solution B obtained by step (1), (2) are merged, recycle ethyl alcohol and is concentrated into appropriate, addition ethyl alcohol
Make alcohol content up to 70%, stir evenly, stand, take supernatant recycling ethyl alcohol and be concentrated, Exocarpium Citri Grandis extracting solution is made；
(4) it takes step (1) volatile oil that the hydroxypropyl-β-cyclodextrin that average substitution degree is 4.5 is added to be included, be wrapped
Close liquid, wherein volatile oil and the inventory envelope-bulk to weight ratio of hydroxypropyl-β-cyclodextrin are 1:10；
(5) liquid will be included obtained by Exocarpium Citri Grandis extracting solution obtained by above-mentioned steps (3) and step (4), it is mixed with 700ml water for injection
It closes uniformly, osmotic pressure regulator glucose 35g, corrigent lemon extract 0.5ml, sodium hydroxide solution is added, and add injection
With water to 1000ml, mixing, filtration, encapsulating, sterilizing.The pH value of obtained Exocarpium Citri Grandis atomized inhalation is 6.0, and medical fluid is uniform
Clarification.
Embodiment 2
It is specific as follows the present embodiment provides a kind of Exocarpium Citri Grandis atomized inhalation and preparation method thereof:
(1) Exocarpium Citri Grandis 200g is taken, 8 times of amount water are added, heating decocts 2 hours, and collects volatile oil, non-volatile extraction product,
Non-volatile extraction product is filtered, extracting solution A, the dregs of a decoction are obtained；
(2) dregs of a decoction add 6 times of amount water again, and heating decocts 2 hours, and filtering obtains extracting solution B；
(3) extracting solution A, extracting solution B obtained by step (1), (2) are merged, recycle ethyl alcohol and is concentrated into appropriate, addition ethyl alcohol
Make alcohol content up to 70%, stir evenly, stand, take supernatant recycling ethyl alcohol and be concentrated, Exocarpium Citri Grandis extracting solution is made；
(4) hydroxypropyl-β-cyclodextrin that average substitution degree is 4.5 is added in the volatile oil of step (1) to include, is obtained
Include liquid, wherein volatile oil and the inventory envelope-bulk to weight ratio of hydroxypropyl-β-cyclodextrin are 1:10；
(5) above-mentioned steps (3) Exocarpium Citri Grandis extracting solution and step (4) are included into liquid, are uniformly mixed with 700ml water for injection,
Osmotic pressure regulator glucose 35g, corrigent lemon extract 0.5ml, sodium hydroxide solution is added, and mends and injects water to
1000ml, mixing, filtration, encapsulating, sterilizing.The pH value of obtained Exocarpium Citri Grandis atomized inhalation is 4.5, and medical fluid is uniformly clarified.
Embodiment 3
It is specific as follows the present embodiment provides a kind of Exocarpium Citri Grandis atomized inhalation and preparation method thereof:
(1) Exocarpium Citri Grandis 200g is taken, 8 times of amount water are added, heating decocts 2 hours, and collects volatile oil, non-volatile extraction product,
Non-volatile extraction product is filtered, extracting solution A, the dregs of a decoction are obtained；
(2) dregs of a decoction add 6 times of amount water again, and heating decocts 2 hours, and filtration obtains extracting solution B；
(3) extracting solution A, extracting solution B obtained by step (1), (2) are merged, recycle ethyl alcohol and is concentrated into appropriate, addition ethyl alcohol
Make alcohol content up to 70%, stir evenly, stand, take supernatant recycling ethyl alcohol and be concentrated, Exocarpium Citri Grandis extracting solution is made；
(4) it takes step (1) volatile oil that the hydroxypropyl-β-cyclodextrin that average substitution degree is 10.0 is added to be included, obtain
Include liquid, wherein volatile oil and the inventory envelope-bulk to weight ratio of hydroxypropyl-β-cyclodextrin are 1:10；
(5) Exocarpium Citri Grandis extracting solution obtained by above-mentioned steps (3) and step (4) are included into liquid, is mixed with 700ml water for injection
It is even, osmotic pressure regulator glucose 35g, corrigent lemon extract 0.5ml, sodium hydroxide solution is added, and add water for injection
To 1000ml, mixing, filtration, encapsulating, sterilizing.The pH value of obtained Exocarpium Citri Grandis atomized inhalation is 6.0, and medical fluid is uniformly clear
Clearly.
Embodiment 4
It is specific as follows the present embodiment provides a kind of Exocarpium Citri Grandis atomized inhalation and preparation method thereof:
(1) Exocarpium Citri Grandis 300g is taken, 12 times of amount water are added, heating decocts 2 hours, and collects distillate, non-distillation extraction product,
It filters non-distillation and extracts product, obtain extracting solution A, the dregs of a decoction；
(2) dregs of a decoction add 6 times of 5% ethanol solution again, and heating decocts 2 hours, and filtering obtains extracting solution B；
(3) extracting solution A, extracting solution B obtained by step (1), (2) are merged, recycle ethyl alcohol and is concentrated into appropriate, addition ethyl alcohol
Make alcohol content up to 50%, stir evenly, stand, take supernatant recycling ethyl alcohol and be concentrated, Exocarpium Citri Grandis extracting solution is made；
(4) it takes step (1) distillate that the hydroxypropyl-β-cyclodextrin that average substitution degree is 2.0 is added to be included, be wrapped
Liquid is closed, wherein distillate and the inventory envelope-bulk to weight ratio of hydroxypropyl-β-cyclodextrin are 100:10；
(5) liquid will be included obtained by Exocarpium Citri Grandis extracting solution obtained by above-mentioned steps (3) and step (4), it is mixed with 600ml physiological saline
It closes uniformly, osmotic pressure regulator calcium chloride 2g, corrigent orange flavor 0.4ml, potassium hydroxide solvent is added, and add physiology salt
Water is to 1000ml, mixing, filtration, encapsulating, sterilizing.The pH value of obtained Exocarpium Citri Grandis atomized inhalation is 6.5, and medical fluid is uniformly clear
Clearly.
Stability test is the results show that Exocarpium Citri Grandis atomized inhalation obtained by the present embodiment is accelerating in 6 months except volatilization
Property component content be slightly decreased outer, other quality control indexs are basicly stable.
Embodiment 5
It is specific as follows the present embodiment provides a kind of Exocarpium Citri Grandis atomized inhalation and preparation method thereof:
(1) Exocarpium Citri Grandis 300g is taken, 12 times of amount water are added, heating decocts 2 hours, and collects distillate, non-distillation extraction product,
It filters non-distillation and extracts product, obtain extracting solution A, the dregs of a decoction；
(2) dregs of a decoction add 6 times of 20% ethanol solution again, and heating decocts 2 hours, and filtering obtains extracting solution B；
(3) extracting solution A, extracting solution B obtained by step (1), (2) are merged, recycle ethyl alcohol and is concentrated into appropriate, addition ethyl alcohol
Make alcohol content up to 85%, stir evenly, stand, take supernatant recycling ethyl alcohol and be concentrated, Exocarpium Citri Grandis extracting solution is made；
(4) it takes step (1) distillate that the hydroxypropyl-β-cyclodextrin that average substitution degree is 5.0 is added to be included, be wrapped
Liquid is closed, wherein distillate and the inventory envelope-bulk to weight ratio of hydroxypropyl-β-cyclodextrin are 100:1；
(5) liquid will be included obtained by Exocarpium Citri Grandis extracting solution obtained by above-mentioned steps (3) and step (4), it is mixed with 600ml physiological saline
It closes uniformly, osmotic pressure regulator calcium chloride 2g, corrigent orange flavor 0.4ml, potassium hydroxide solvent is added, and add physiology salt
Water is to 1000ml, mixing, filtration, encapsulating, sterilizing.The pH value of obtained Exocarpium Citri Grandis atomized inhalation is 6.0, and medical fluid is uniformly clear
Clearly.
Stability test is the results show that Exocarpium Citri Grandis atomized inhalation obtained by the present embodiment has good stability.
Embodiment 6
It is specific as follows the present embodiment provides a kind of Exocarpium Citri Grandis atomized inhalation and preparation method thereof:
(1) Exocarpium Citri Grandis 300g is taken, 10 times of amount water are added, heating decocts 2 hours, and collects distillate, non-distillation extraction product,
It filters non-distillation and extracts product, obtain extracting solution A, the dregs of a decoction；
(2) dregs of a decoction add 8 times of amount water again, and heating decocts 2 hours, and filtering obtains extracting solution B；
(3) extracting solution A, extracting solution B obtained by step (1), (2) merged, be concentrated into right amount, ethyl alcohol, which is added, reaches alcohol content
65%, it stands, takes supernatant, recycle ethyl alcohol and be concentrated, Exocarpium Citri Grandis extracting solution is made；
(4) mixed with 600ml water for injection by distillate obtained by Exocarpium Citri Grandis extracting solution obtained by above-mentioned steps (3) and step (1)
It closes uniformly, osmotic pressure regulator sodium chloride 7g, corrigent orange flavor 0.4ml, sodium bicarbonate solution is added, and add injection
Water is to 1000ml, mixing, filtration, encapsulating, sterilizing.The pH value of obtained Exocarpium Citri Grandis atomized inhalation is 7.5, and medical fluid is uniformly clear
Clearly.
Stability test is the results show that Exocarpium Citri Grandis atomized inhalation obtained by the present embodiment is accelerating in 6 months except volatilization
Property component content declined outer, other quality control indexs are basicly stable.
Embodiment 7
It is specific as follows the present embodiment provides a kind of Exocarpium Citri Grandis atomized inhalation and preparation method thereof:
(1) Exocarpium Citri Grandis 600g is taken, adds 6 times of 60% ethanol solutions of amount, heating decocts 1 hour, and collects volatile oil, non-volatile
Product is extracted, non-volatile extraction product is filtered, obtains extracting solution A, the dregs of a decoction；
(2) dregs of a decoction add 4 times of 50% ethanol solutions of amount again, and heating decocts 1 hour, and filtering obtains extracting solution B；
(3) extracting solution A, extracting solution B obtained by step (1), (2) are merged, recycle ethyl alcohol and are concentrated, Exocarpium Citri Grandis is made and extracts
Liquid；
(4) it by Exocarpium Citri Grandis extracting solution obtained by above-mentioned steps (3), is uniformly mixed with 500ml water for injection, osmotic pressure tune is added
Agent mannitol 20g, corrigent lemon extract 0.5ml, sodium hydroxide solution are saved, and mends and injects water to 1000ml, is mixed, filter
It crosses, encapsulating, sterilizing.The pH value of obtained Exocarpium Citri Grandis atomized inhalation is 8.5, and medical fluid is uniformly clarified.
Stability test is the results show that Exocarpium Citri Grandis atomized inhalation obtained by the present embodiment has good stability.
Embodiment 8
It is specific as follows the present embodiment provides a kind of Exocarpium Citri Grandis atomized inhalation and preparation method thereof:
(1) Exocarpium Citri Grandis 100g is taken, 10 times of amount water are added, heating decocts 2 hours, and collects volatile oil, non-volatile extraction product,
Non-volatile extraction product is filtered, extracting solution A, the dregs of a decoction are obtained；
(2) dregs of a decoction add 5 times of 95% ethanol solutions of amount again, and heating decocts 1 hour, and filtering obtains extracting solution B；
(3) extracting solution A, extracting solution B obtained by step (1), (2) are merged, recycle ethyl alcohol and is concentrated into appropriate, addition ethyl alcohol
Make alcohol content up to 80%, stir evenly, stand, take supernatant recycling ethyl alcohol and be concentrated, Exocarpium Citri Grandis extracting solution is made；
(4) it takes step (1) volatile oil that the hydroxypropyl-β-cyclodextrin that average substitution degree is 4.0 is added to be included, be wrapped
Liquid is closed, wherein distillate and the inventory envelope-bulk to weight ratio of hydroxypropyl-β-cyclodextrin are 1:1；
(4) liquid will be included obtained by Exocarpium Citri Grandis extracting solution obtained by above-mentioned steps (3) and step (4), it is mixed with 800ml physiological saline
It closes uniformly, osmotic pressure regulator glucose 100g, corrigent menthol 0.1g, sodium hydroxide solution is added, and add injection
Water is to 1000ml, mixing, filtration, encapsulating, sterilizing.The pH value of obtained Exocarpium Citri Grandis atomized inhalation is 6.0, and medical fluid is uniformly clear
Clearly.
Stability test is the results show that Exocarpium Citri Grandis atomized inhalation obtained by the present embodiment has good stability.
Test example 1: the stability of Exocarpium Citri Grandis atomized inhalation compares
Exocarpium Citri Grandis atomized inhalation made from embodiment 1, embodiment 2 and embodiment 3 is placed in stability test case, in
It 40 DEG C ± 2 DEG C, is placed 6 months under conditions of relative humidity 75% ± 5%, the accelerated stability for carrying out product is investigated, and is as a result seen
Shown in the following table 1.
It can be seen that Exocarpium Citri Grandis atomized inhalation produced by the present invention from investigation result and have certain stability.Wherein,
Inhalant optimal stability obtained by embodiment 1 accelerates quality in 6 months to have no significant change；The obtained sucking of embodiment 2
Agent accelerates preceding 3 months its characters to be also able to maintain clarification, until there is slight turbid after accelerating 6 months, the reason is that the pH of the solution
It is worth relatively low, shows to adjust pH value to a certain range, facilitate the stability for extending Exocarpium Citri Grandis atomized inhalation；Embodiment 3 is made
The content of major volatile constituents limonene in inhalant is obtained lower than sample size obtained by another two embodiment, and accelerates 6
Limonene content decline 15.98% after month, the reason is that hydroxypropyl-β-cyclodextrin average substitution degree used in embodiment 3 is higher, table
The bright hydroxypropyl-β-cyclodextrin using appropriate degree of substitution helps to improve the inclusion rate and stability of Exocarpium Citri Grandis volatile component.
The stability of 1 Exocarpium Citri Grandis aerosol inhalation solution of table compares
Test example 2: the external atomization evaluation of Exocarpium Citri Grandis atomized inhalation
(1) delivery rate and delivering total amount measurement
Method: referring to method under version " Chinese Pharmacopoeia " four " sucking preparation " (general rule 0111) items in 2015, with aurantiin
It is measured for Testing index.
Instrument: respiration simulator, model BRS2000 (COPLEY company, Britain)；403H compressed air type atomizer (Jiangsu
Fish dive Medical Devices limited liability company).
Sample: Exocarpium Citri Grandis atomized inhalation 5ml (its naringin content 5.66mg/ml) obtained by embodiment 1.
As a result: can be seen that Exocarpium Citri Grandis atomized inhalation produced by the present invention in adult and children from the result of the following table 2
Delivering total amount respectively reached 82.9% and 56.3% in terms of aurantiin, and effectively nebulisation time shows that this is molten in 10min
Liquid has good atomization.
Table 2 Exocarpium Citri Grandis aerosol inhalation solution delivery rate and delivering total amount measurement result in terms of aurantiin
| The respiratory characteristic of respiration simulator | It is adult | Children |
| Tidal volume (ml) | 500 | 155 |
| Respiratory rate (circulation/min) | 15 | 25 |
| Respiratory waveform | Sinusoidal | Sinusoidal |
| Respiratory quotient | 1:1 | 1:2 |
| Delivery rate (mg/min) | 2.98 | 1.67 |
| It delivers total amount (mg) | 23.47 | 15.92 |
| Deliver percentage | 82.9% | 56.3% |
| Effective nebulisation time (min) | 7.88 | 9.53 |
(2) aerodynamic size Evaluation on distribution
Method: referring to version " Chinese Pharmacopoeia " four " minuteness particle air dynamic behaviour measuring method " (general rules in 2015
0111) method under item, is measured by Testing index of aurantiin.
Instrument: particle collision collector of new generation, model NGI-1104 (COPLEY company, Britain)；402AI ultrasonic fog
Change device (Jiangsu Yuyue Medical Equipment Inc).
Sample: Exocarpium Citri Grandis aerosol inhalation solution 5ml (its naringin content 5.66mg/ml) obtained by embodiment 1.
As a result: can be seen that the air of Exocarpium Citri Grandis aerosol inhalation solution produced by the present invention from the result of the following table 3 and Fig. 1
Minuteness particle dosage of the aerodynamic particle size less than 5 μm reaches 15.35mg, the total medication amount of 66.13% and Zhan of the total deposition of Zhan
54.24%；The mass median aerodynamic partial size of solution is 4.879 μm.Illustrate majority of particles diameter after the solution atomization
Less than 5 μm, it can be effectively deposited on respiratory tract and lung, play preferable therapeutic effect.
The aerodynamic size measure of spread result of the Exocarpium Citri Grandis aerosol inhalation solution in terms of aurantiin of table 3
| Index | Measurement result |
| Total deposition | 23.21mg |
| ≤ 5 μm of minuteness particle dosage | 15.35mg |
| ≤ 5 μm of minuteness particle scores | 66.13% |
| Mass median aerodynamic partial size | 4.879μm |
| Geometric standard deviation | 2.02 |
Comparative example 1
This example is the comparative example of embodiment 1, compared with Example 1, the difference is that pH adjusting agent is not added, specifically such as
Under:
(1) Exocarpium Citri Grandis 200g is taken, 8 times of amount water are added, heating decocts 2 hours, and collects volatile oil, non-volatile extraction product,
Non-volatile extraction product is filtered, extracting solution A, the dregs of a decoction are obtained；
(2) dregs of a decoction add 6 times of amount water again, and heating decocts 2 hours, and filtering obtains extracting solution B；
(3) extracting solution A, extracting solution B obtained by step (1), (2) are merged, recycle ethyl alcohol and is concentrated into appropriate, addition ethyl alcohol
Make alcohol content up to 70%, stir evenly, stand, take supernatant recycling ethyl alcohol and be concentrated, Exocarpium Citri Grandis extracting solution is made；
(4) it takes step (1) volatile oil that the hydroxy propyl-Beta cyclodextrin that average substitution degree is 4.5 is added to be included, be wrapped
Close liquid, wherein the inventory envelope-bulk to weight ratio of volatile oil and cyclodextrin is 1:10；
(5) liquid will be included obtained by Exocarpium Citri Grandis extracting solution obtained by above-mentioned steps (3) and step (4), it is mixed with 700ml water for injection
It closes uniformly, osmotic pressure regulator glucose 35g, corrigent lemon extract 0.5ml is added, and mend and inject water to 1000ml,
Mixing, filtration, encapsulating, sterilizing.The pH value of obtained Exocarpium Citri Grandis atomized inhalation is 3.8, and medical fluid occurs after room temperature 12h
Insoluble matter, solution are muddy.
Each technical characteristic of embodiment described above can be combined arbitrarily, for simplicity of description, not to above-mentioned reality
It applies all possible combination of each technical characteristic in example to be all described, as long as however, the combination of these technical characteristics is not deposited
In contradiction, all should be considered as described in this specification.
The embodiments described above only express several embodiments of the present invention, and the description thereof is more specific and detailed, but simultaneously
It cannot therefore be construed as limiting the scope of the patent.It should be pointed out that coming for those of ordinary skill in the art
It says, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to protection of the invention
Range.Therefore, the scope of protection of the patent of the invention shall be subject to the appended claims.
Claims (10)
1. a kind of sucking preparation, which is characterized in that the sucking preparation includes active constituent Exocarpium Citri Grandis extract, is suitable for inhaling
Enter the pharmaceutic adjuvant of administration；The Exocarpium Citri Grandis extract is the extracting solution of Exocarpium Citri Grandis or the volatile oil of Exocarpium Citri Grandis and change tangerine
The mixture of the extracting solution of the mixture of red extracting solution or the distillate of Exocarpium Citri Grandis and Exocarpium Citri Grandis；
Exocarpium Citri Grandis extract included in sucking preparation described in every 100ml is prepared by 10g~60g Exocarpium Citri Grandis；Institute
The pH value for stating sucking preparation is adjusted to 4.0~8.5 using pH adjusting agent.
2. sucking preparation according to claim 1, which is characterized in that the pH value of the sucking preparation uses pH adjusting agent tune
To 5.0~7.5.
3. sucking preparation according to claim 1, which is characterized in that the pharmaceutic adjuvant includes cyclodextrin.
4. sucking preparation according to claim 3, which is characterized in that the cyclodextrin be average substitution degree be 2.0~
10.0 hydroxypropyl-β-cyclodextrin.
5. sucking preparation according to any one of claims 1 to 4, which is characterized in that the pharmaceutic adjuvant includes osmotic pressure
Regulator, corrigent, solvent；The pH adjusting agent selects at least one of sodium hydroxide, potassium hydroxide, sodium bicarbonate.
6. sucking preparation according to any one of claims 1 to 4, which is characterized in that the volatile oil of the Exocarpium Citri Grandis changes tangerine
The extracting solution of red distillate, Exocarpium Citri Grandis is prepared via a method which:
(1) Exocarpium Citri Grandis is taken, adding water, perhaps ethanol solution decocts collection volatile oil or distillate, non-volatile/non-distillation are extracted and produced
Object；It filters non-volatile/non-distillation and extracts product, obtain extracting solution A, the dregs of a decoction；
(2) dregs of a decoction are taken, water or ethanol solution is added to decoct, filtering obtains extracting solution B；
(3) merge the extracting solution A, the extracting solution B, Exocarpium Citri Grandis extracting solution is made in concentration.
7. sucking preparation according to claim 6, which is characterized in that the envelope-bulk to weight ratio of the volatile oil and cyclodextrin is
1:(1~10)；The envelope-bulk to weight ratio of the distillate and cyclodextrin is 100:(1~10).
8. the preparation method of the described in any item sucking preparations of claim 1 to 7, which comprises the steps of: taking
Pharmaceutic adjuvant, mixing, filtration, encapsulating, sterilizing is added in Exocarpium Citri Rubrum extract；The pH value of the sucking preparation uses pH adjusting agent tune
To 4.0~8.5；Wherein, the Exocarpium Citri Grandis extract is the extracting solution of Exocarpium Citri Grandis or the volatile oil and Exocarpium Citri Grandis of Exocarpium Citri Grandis
The mixture of extracting solution or the distillate of Exocarpium Citri Grandis and Exocarpium Citri Grandis extracting solution mixture.
9. the preparation method of sucking preparation according to claim 8, which is characterized in that include ring in the pharmaceutic adjuvant
Dextrin, then the preparation method includes the following steps:
(1) volatile oil of Exocarpium Citri Grandis or the distillate of Exocarpium Citri Grandis are taken, cyclodextrin is added and is included, inclusion liquid is made；
(2) extracting solution for mixing the inclusion liquid, Exocarpium Citri Grandis, is added pharmaceutic adjuvant, mixing, filtration, encapsulating, sterilizing；The suction
The pH value for entering preparation is adjusted to 4.0~8.5 using pH adjusting agent.
10. sucking preparation described in claim 1 to 7 is in treatment flu, influenza, urgency/pharyngo-laryngitis chronica, urgency/chronic bronchial
Inflammation, urgency/chronic bronchitis, Chronic Obstructive Pulmonary Disease, bronchial asthma, bronchiectasis, pneumonia, pulmonary emphysema and pulmonary fibrosis
Caused cough, expectoration, the application in asthma.
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| CN110327313A (en) * | 2019-06-21 | 2019-10-15 | 中山大学 | A kind of naringenin aerosol inhalation solution preparation and preparation method thereof |
| CN114209772A (en) * | 2021-12-21 | 2022-03-22 | 浙江中创雾联生物科技有限公司 | Pummelo peel atomized liquid and preparation method thereof |
| WO2023088499A1 (en) * | 2022-10-26 | 2023-05-25 | 中山大学 | Use of shaddock oil in preparation of product for protecting epithelial barrier and repairing damaged functions of pharyngeal mucosa |
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