CN115531359A - Isoniazid inhalation solution and preparation method and application thereof - Google Patents

Isoniazid inhalation solution and preparation method and application thereof Download PDF

Info

Publication number
CN115531359A
CN115531359A CN202211207369.0A CN202211207369A CN115531359A CN 115531359 A CN115531359 A CN 115531359A CN 202211207369 A CN202211207369 A CN 202211207369A CN 115531359 A CN115531359 A CN 115531359A
Authority
CN
China
Prior art keywords
isoniazid
inhalation solution
water
inhalation
solution according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202211207369.0A
Other languages
Chinese (zh)
Inventor
任恒春
李俊霞
赵梦晴
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zhengzhou Shenlanhai Biomedical Technology Co ltd
Original Assignee
Zhengzhou Shenlanhai Biomedical Technology Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zhengzhou Shenlanhai Biomedical Technology Co ltd filed Critical Zhengzhou Shenlanhai Biomedical Technology Co ltd
Priority to CN202211207369.0A priority Critical patent/CN115531359A/en
Publication of CN115531359A publication Critical patent/CN115531359A/en
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A61P31/06—Antibacterial agents for tuberculosis

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pulmonology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Molecular Biology (AREA)
  • Otolaryngology (AREA)
  • Dispersion Chemistry (AREA)
  • Biochemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention relates to an isoniazid inhalation solution, a preparation method and application thereof. The invention has the advantages that the medicine directly acts on the lung through oral and nasal inhalation, can be gathered into higher concentration in the lung and enters a respiratory and blood circulatory system, thereby achieving the purpose of whole body medication, and the inhalation preparation greatly reduces the metabolic process of the medicine by liver and kidney and greatly reduces the damage to the liver and kidney of a patient.

Description

Isoniazid inhalation solution and preparation method and application thereof
Technical Field
The invention belongs to the field of medicinal preparations, and particularly relates to an isoniazid inhalation solution, and a preparation method and application thereof.
Background
Isoniazid (Isoniazid), chemical name: 4-pyridine carbohydrazide, together with rifampicin, ethambutol and pyrazinamide, are first-line antituberculosis drugs. Isoniazid was invented in 1952 as a chemical drug, which has fundamentally changed the treatment of tuberculosis, and most doctors still consider it to be an indispensable main drug for the treatment of tuberculosis in the history of about 70 years although some patients have developed drug resistance to tubercle bacillus infected with isoniazid. Isoniazid has the following structural formula:
Figure BDA0003874570700000011
the isoniazid injection is firstly marketed in Japan in 1960, and has the characteristics of obvious curative effect on tuberculosis and less adverse reaction for more than 50 years. The isoniazid injection has the characteristics of quick response and quick disease stabilization for serious tuberculosis patients who can not take oral drugs. The traditional Chinese medicine composition is still used in developed countries such as Europe, america, japan and the like, still remains a first-line clinical medicine in extensive developing countries, and has low clinical treatment cost, definite curative effect and irreplaceability. However, in the clinical research and drug development process, we also find that the prepared isoniazid injection is extremely unstable, and has no high absorption rate and safe administration for oral administration due to the poor control of free hydrazine in isoniazid.
Currently, various studies are being conducted on isoniazid formulations, such as the development of new dosage forms. The aerosol inhalation preparation is a special formulation which is administrated through the lung, can quickly and directly enter the lung to exert the drug effect through a local administration mode, reduces the administration dosage, improves the drug curative effect, has better treatment advantages on respiratory system diseases such as asthma, COPD, respiratory tract infection, cystic fibrosis, pulmonary heart disease, pulmonary hypertension and the like, is particularly convenient for children, old people and serious patients to take, and is written into expert consensus and diagnosis and treatment guidelines for many times. However, there are still some problems with the currently marketed aerosolized inhalation formulations, such as: poor compliance caused by more administration times, inaccurate dosage, low atomization efficiency, high impurity content and the like.
Disclosure of Invention
In order to overcome the problems in the prior art, the invention provides an isoniazid inhalation solution, a preparation method and application thereof, the isoniazid inhalation solution is directly acted on the lung through oral and nasal inhalation, can be aggregated into higher concentration in the lung and enters a respiratory and blood circulation system, thereby achieving the purpose of systemic medication, and the problem of high impurity content of the preparation can be improved by using citric acid as a pH regulator.
The specific technical scheme provided by the invention is as follows:
an isoniazid inhalation solution, which comprises isoniazid, an osmotic pressure regulator, a pH regulator and water.
By the technical scheme, the isoniazid inhalation solution can replace oral administration and other dosage forms, is directly inhaled from the mouth and the nose, avoids the first pass effect of the liver and the damage and degradation of gastrointestinal tracts, can be gathered into higher concentration in the lung, and then enters a respiratory and blood circulation system, so that the purpose of whole body treatment is achieved, the metabolic process of the liver and the kidney to the medicine is greatly reduced, and the liver and kidney damage to a patient is greatly reduced; further fills the blank of the current domestic and foreign markets, provides a novel, safe and effective drug delivery mode for isoniazid, and provides a brand new solution for the treatment of pulmonary tuberculosis.
Furthermore, the single dose of the inhalation solution comprises 100-200 mg of isoniazid, 10-30 mg of osmotic pressure regulator, (0.3-0.5%) of pH regulator and (1-2 g) of water according to parts by weight.
Through the technical scheme, the composition is simple, the pH value control range meets the safety requirement of clinical medication, and meanwhile, the osmotic pressure is close to isotonic, so that bronchospasm and cough caused by inhalation of isoniazid solution can be reduced; the prepared preparation has stable quality and high atomization efficiency, and the quality is not lower than that of the original injection on the market; in the formula, a mild pH regulator is adopted to regulate the pH, the attack of hydrochloric acid serving as a pH regulator proton on a hydrazine group is relatively reduced, the hydrolysis of isoniazid can be greatly slowed down, and the generation of toxic impurities is reduced.
Furthermore, the osmolality of the inhalation solution is 270 mOsm/L-310 mOsm/L, and the clinical medication requirement is met.
Further, the osmotic pressure regulator is one or more of sodium chloride, potassium chloride and mannitol.
Further, the pH regulator is one or more of sodium hydroxide, hydrochloric acid, sodium dihydrogen phosphate, citric acid and sodium citrate, and preferably citric acid.
Further, the water is selected from drinking water, purified water or water for injection.
Furthermore, after the isoniazid inhalation solution is atomized by a PARI PlusTM compression atomizer, the aerodynamic mass median diameter is 2-5 μm, the percentage of fine particles is 30% -70%, and the administration time after atomization is 10-30min.
The invention also provides a preparation method of the isoniazid inhalation solution, which comprises the following steps:
s1, preparing a liquid according to the raw material ratio; dissolving an osmotic pressure regulator in water with the volume constant of 80-90% and the temperature of 30-60 ℃, and stirring until the osmotic pressure regulator is completely dissolved to form an aqueous solution; adding isoniazid into the aqueous solution, stirring until the isoniazid is completely dissolved, adding a pH regulator to regulate the pH to 6-7, and further preferably 6.3-6.7, and uniformly stirring;
s2, fixing the volume; adding water to the total volume in the step S1, and uniformly stirring to prepare an intermediate liquid medicine;
s3, detecting quality;
s4, filtering and encapsulating; filtering qualified intermediate liquid medicine by 0.45-micrometer and 0.22-micrometer filters in sequence, adopting blowing, filling and sealing integrated filling and sealing equipment, and filling into 2ml polyethylene plastic ampoule bottles;
by adopting the technical scheme, the isoniazid inhalation solution provided by the invention is single dose, adopts polyethylene packaging and sterilization filtration processes, can greatly improve the impurity level of the preparation, is convenient and safe in clinical use process, and better improves the adaptability of patients; moreover, the whole preparation process is simple, the equipment cost is low, and the industrial production is facilitated.
Further, in step S1, the pipe is flushed with 0.02 to 0.05% EDTA-2Na before the solution is prepared.
By the technical scheme, the isoniazid inhalation solution is sensitive to metal ions, so that the pipeline is flushed by 0.02-0.05% of EDTA-2Na before the solution preparation is produced, and batch quality difference caused by the metal ions in the production process is prevented.
In addition, the invention provides an application of the isoniazid inhalation solution, namely an application of the isoniazid inhalation solution in preparing a medicine for treating pulmonary tuberculosis infection.
Has the beneficial effects that: (1) Compared with other formulations, the isoniazid inhalation solution is directly inhaled from the mouth and the nose, can be gathered into higher concentration in the lung, and then enters a respiratory and blood circulation system, so that the purpose of whole body treatment is achieved, the liver and kidney damage to a patient is greatly reduced, and the administration is safer; (2) The prescription has simple components, the pH value control range meets the safety requirement of clinical medication, and meanwhile, the osmotic pressure is close to isoosmotic, so that the bronchospasm and cough caused by inhaling isoniazid solution can be reduced; (3) The problem of high impurity content can be solved by selecting citric acid as a pH regulator; (4) The pipeline is flushed by 0.02-0.05% of EDTA-2Na before liquid preparation, so that the quality difference of batch parts caused by metal ions in the production process can be prevented; and (5) the prepared preparation has stable quality and high atomization efficiency.
Detailed Description
The technical solutions of the present invention are described clearly and completely by way of examples, and it is obvious that the described examples are only a part of the examples of the present invention, but not all of the examples. All other embodiments, which can be obtained by a person skilled in the art without making any creative effort based on the embodiments in the present invention, belong to the protection scope of the present invention.
The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially. In the following examples, isoniazid is used in an anhydrous basis.
Example 1
Prescription:
Figure BDA0003874570700000031
Figure BDA0003874570700000041
the preparation process comprises the following steps:
s1, flushing a pipeline by using 0.02% of EDTA-2Na, and preparing a liquid according to the mixture ratio of the raw materials; dissolving sodium chloride in water for injection with the total volume of 90% and the temperature of 30 ℃, and stirring until the sodium chloride is completely dissolved to form an aqueous solution; adding isoniazid into the aqueous solution, stirring until the isoniazid is completely dissolved, then adding 0.5mol/l hydrochloric acid solution to adjust the pH value to 6.7, and stirring uniformly;
s2, fixing the volume; adding water to the full volume in the step S1, and uniformly stirring to prepare an intermediate liquid medicine;
s3, detecting quality;
s4, filtering and encapsulating; and (3) sequentially carrying out coarse filtration with the thickness of 0.45 mu m and fine filtration with the thickness of 0.22 mu m on the intermediate liquid medicine qualified in detection, and filling the intermediate liquid medicine into a 2mL polyethylene plastic ampoule bottle by adopting a BFS sterile filling process.
Examples 2 to 4: preparing preparations with different pH values by selecting 0.5mol/l hydrochloric acid solution
Prescription:
prescription composition Dosage of
Isoniazid 100g
Sodium chloride 20g
0.5mol/l hydrochloric acid solution Adjusting pH to 6.0, 6.5, 7.0
Water for injection To 2L
The preparation process comprises the following steps:
s1, flushing a pipeline by using 0.05% of EDTA-2Na, taking injection water with the prescription amount of 90%, sequentially adding the main drug and the osmotic pressure regulator with the prescription amount, stirring and dissolving, evenly dividing into three parts, adjusting the pH value to 6.0, 6.5 and 7.0 by using 0.5mol/l hydrochloric acid pH regulator, and uniformly stirring;
s2, fixing the volume; respectively adding water into the step S1 to fix the volume to the full volume, and uniformly stirring to prepare an intermediate liquid medicine;
s3, detecting quality;
s4, filtering and encapsulating; and (3) sequentially carrying out coarse filtration with the thickness of 0.45 mu m and fine filtration with the thickness of 0.22 mu m on the intermediate liquid medicine qualified in detection, and filling the intermediate liquid medicine into a 2mL polyethylene plastic ampoule bottle by adopting a BFS sterile filling process.
Examples 5 to 8: preparing different pH preparations by selecting citric acid buffer pH regulator
Prescription:
prescription composition Amount of the composition
Isoniazid 100g
Sodium chloride 20g
Citric acid buffer pH 3.0 Adjusting pH to 6.0, 6.3, 6.7, 7.0
Water for injection Adding to 2L
The preparation process comprises the following steps:
s1, flushing a pipeline by using 0.05% of EDTA-2Na, taking 90% of injection water according to the prescription amount, sequentially adding the main drug and the osmotic pressure regulator according to the prescription amount, stirring and dissolving, averagely and equally dividing into four parts, adjusting the pH value to 6.0, 6.3, 6.7 and 7.0 by using a citric acid buffer solution pH regulator, and uniformly stirring;
s2, fixing the volume; respectively adding water to the step S1 to a constant volume to full volume, and uniformly stirring to prepare an intermediate liquid medicine;
s3, detecting the quality;
s4, filtering and encapsulating; and (3) sequentially carrying out coarse filtration with the thickness of 0.45 mu m and fine filtration with the thickness of 0.22 mu m on the intermediate liquid medicine qualified in detection, and filling the intermediate liquid medicine into a 2mL polyethylene plastic ampoule bottle by adopting a BFS sterile filling process.
Comparative example 1
Prescription:
prescription composition Dosage of
Isoniazid 100g
Sodium chloride 20g
0.5mol/l hydrochloric acid solution Adjusting the pH to 6.6
Water for injection To 2L
The preparation process comprises the following steps:
s1, preparing a liquid according to the raw material ratio; dissolving sodium chloride in water for injection with the total volume of 90% and the temperature of 60 ℃, and stirring until the sodium chloride is completely dissolved to form an aqueous solution; adding isoniazid into the aqueous solution, stirring until the isoniazid is completely dissolved, then adding 0.5mol/l hydrochloric acid solution to adjust the pH value to 6.6, and stirring uniformly;
s2, fixing the volume; adding water to the full volume in the step S1, and uniformly stirring to prepare an intermediate liquid medicine;
s3, detecting quality;
s4, filtering and encapsulating; and (3) sequentially carrying out coarse filtration with the thickness of 0.45 mu m and fine filtration with the thickness of 0.22 mu m on the intermediate liquid medicine qualified in detection, and filling the intermediate liquid medicine into a 2mL polyethylene plastic ampoule bottle by adopting a BFS sterile filling process.
Test example 1
Taking the samples of the invention in the example 1 and the comparative example 1, examining the stability under the acceleration conditions of 40 ℃ +/-2 ℃ and RH25% +/-5%, sampling in 0, 3 and 6 months respectively, and examining the properties, the osmolality, related substances, the water loss rate and the content of the samples, wherein the results are shown in Table 1. The content and related substance determination method refers to the content determination and related substance determination method under the entry registration standard item of the raw material medicines and the injection of isoniazid of USP43-NF38 and European pharmacopoeia EP10.0, the limit of the content determination is 95.0-105.0%, and the limit of the total impurities of the related substances is assumed to be 2.0%.
TABLE 1 comparison of the stability and impurity content of the formulations
Figure BDA0003874570700000061
And (4) analyzing results: from the above comparison results, it can be seen that the product is stable to oxygen and can reduce impurities by flushing the pipeline with 0.02-0.05% ED TA-2Na before dispensing.
Test example 2
Taking samples with different pH values in comparative example 1 and examples 2-8 of the invention, examining the stability under the acceleration conditions of 40 +/-2 ℃ and 25% +/-5% RH, respectively sampling in 0, 3 and 6 months, and examining the properties, pH values, related substances and contents of the samples, and the results are shown in Table 2.
TABLE 2 comparison of stability of samples of formulations at different pH
Figure BDA0003874570700000071
Figure BDA0003874570700000081
Figure BDA0003874570700000091
And (4) analyzing results: comparing the stability research results of different pH preparations, the product is formulated by selecting a pH regulator as a citric acid buffer solution, and the pH range of the preparation is controlled to be 6-7.
Test example 3
Using a German Bailey PARI BOY compression nebulizer, 2ml of the inventive comparative example 1 and example 8 samples were taken and the parameters of nebulization time, delivery rate and total delivered amount, percent fine particles FPF (%) and aerodynamic mass median diameter MMAD (. Mu.m) were recorded and the results are given in Table 4.
Figure BDA0003874570700000092
Note {1}: aerodynamic mass median diameter (MMAD): when the total mass of particles of various sizes smaller than a certain aerodynamic diameter in the particulate matter accounts for 50% of the total particulate matter mass (i.e., the sum of all particles of different sizes), the diameter is referred to as mass median diameter.
Note {2}: FPF (%): the deposition rate of the drug in the lungs.
And (4) analyzing results: the isoniazid aerosol inhalation solution prepared by the method has good atomization characteristics, the aerosol inhalation administration time can be controlled within 10-20min, the diameter in aerodynamic quality is 2-5 mu m, the percentage of fine particles is 30% -70%, the requirement of aerosol inhalation can be met, and the optimized prescription (embodiment 8) is obviously superior to the original prescription (comparative example 1).
Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments or portions thereof without departing from the spirit and scope of the invention.

Claims (11)

1. An isoniazid inhalation solution, which is characterized by comprising isoniazid, an osmotic pressure regulator, a pH regulator and water.
2. An isoniazid inhalation solution according to claim 1, wherein the inhalation solution comprises, in parts by weight, 100 to 200mg of isoniazid, 10 to 30mg of an osmotic pressure regulator, (0.3% to 0.5%) of a pH regulator, and (1 g to 2 g) of water.
3. The isoniazid inhalation solution of claim 1, wherein the osmolality of the inhalation solution is 270-310 mOsm/L.
4. Isoniazid inhalation solution according to claim 1, characterized in that the tonicity modifier is one or more of sodium chloride, potassium chloride, mannitol.
5. An isoniazid inhalation solution according to claim 1, characterized in that the pH adjusting agent is one or more of sodium hydroxide, hydrochloric acid, sodium dihydrogen phosphate, citric acid and sodium citrate.
6. An isoniazid inhalation solution as claimed in claim 5, characterized in that the pH adjusting agent is citric acid.
7. Isoniazid inhalation solution according to claim 1, characterized in that the water is selected from drinking water, purified water or water for injection.
8. An isoniazid inhalation solution according to claim 1, wherein the isoniazid inhalation solution has an aerodynamic mass median diameter of 2-5 μm and a percentage of fine particles of 30-70% after nebulization with a PARI PlusTM compression nebulizer.
9. A method of preparing an isoniazid inhalation solution according to any one of claims 1 to 8, characterized in that it comprises the following steps:
s1, preparing a liquid according to the raw material ratio; dissolving an osmotic pressure regulator in water with the volume constant of 80-90% and the temperature of 30-60 ℃, and stirring until the osmotic pressure regulator is completely dissolved to form an aqueous solution; adding isoniazid into the aqueous solution, stirring until the isoniazid is completely dissolved, adding a pH regulator to regulate the pH to 6-7, preferably 6.3-6.7, and uniformly stirring;
s2, fixing the volume; adding water to the total volume in the step S1, and uniformly stirring to prepare an intermediate liquid medicine;
s3, detecting the quality;
s4, filtering and encapsulating; and filtering qualified intermediate liquid medicine by using 0.45-micron and 0.22-micron filters in sequence, adopting blowing, filling and sealing integrated filling and sealing equipment, and filling into a 2ml polyethylene plastic ampoule bottle.
10. The method for preparing an isoniazid inhalation solution according to claim 9, wherein in step S1, the tube is flushed with 0.02 to 0.05% of EDTA-2Na before the solution preparation.
11. Use of isoniazid inhalation solution according to any one of claims 1 to 10 for the preparation of a medicament for the treatment of mycobacterium tuberculosis infection of the lung.
CN202211207369.0A 2022-09-30 2022-09-30 Isoniazid inhalation solution and preparation method and application thereof Pending CN115531359A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202211207369.0A CN115531359A (en) 2022-09-30 2022-09-30 Isoniazid inhalation solution and preparation method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202211207369.0A CN115531359A (en) 2022-09-30 2022-09-30 Isoniazid inhalation solution and preparation method and application thereof

Publications (1)

Publication Number Publication Date
CN115531359A true CN115531359A (en) 2022-12-30

Family

ID=84731338

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202211207369.0A Pending CN115531359A (en) 2022-09-30 2022-09-30 Isoniazid inhalation solution and preparation method and application thereof

Country Status (1)

Country Link
CN (1) CN115531359A (en)

Similar Documents

Publication Publication Date Title
EP0734249B3 (en) Novel and improved aminoglycoside formulation for aerosolization
CN101606903A (en) A kind of atomizing of ambroxol sucks with solution and preparation method thereof
CN102924302A (en) Injection-grade ambroxol hydrochloride and solution for inhalation of injection-grade ambroxol hydrochloride
CN106974898B (en) Solution preparation for acute bronchitis aerosol inhalation and preparation method thereof
WO2021068961A1 (en) Inhalation solution pharmaceutical composition and preparation method therefor
WO2019119720A1 (en) Fudosteine solution preparation for aerosol inhalation, and preparation method therefor
CN107296803A (en) A kind of suction salbutamol sulfate solution and preparation method thereof
CN108159026B (en) Stable ambroxol hydrochloride solution for inhalation and preparation method thereof
CN112402400B (en) Salbutamol sulfate atomized inhalation solution and preparation process and application thereof
CN114053216A (en) A umeclidinium bromide solution preparation for inhalation and its preparation method
CN109260180A (en) A kind of moxifloxacin hydrochloride Neulized inhalation pharmaceutical solutions and preparation method thereof
CN115531359A (en) Isoniazid inhalation solution and preparation method and application thereof
CN114796168A (en) Carbocisteine aerosol inhalation solution preparation and preparation method thereof
WO2022135331A1 (en) Stable liquid pharmaceutical composition containing kuding saponin compound
CN110693861A (en) Terbutaline sulfate solution preparation for aerosol inhalation and preparation method thereof
CN115054573A (en) Salbutamol sulfate injection and preparation method thereof
CN115944609A (en) Isoniazid inhalation solution and preparation method and application thereof
CN114948914B (en) Moxifloxacin hydrochloride solution for aerosol inhalation and preparation method thereof
CN113995721A (en) Ambroxol hydrochloride oral spray solution and preparation method thereof
CN111110634A (en) Chloroquine phosphate inhalation aerosol and preparation method thereof
CN115337311B (en) A composition for treating respiratory system diseases and its preparation method
CN117205186A (en) Leifenacin inhalation spray and preparation method thereof
CN115137713A (en) Amphotericin B atomization inhalation preparation and preparation method thereof
CN113491676B (en) Solution for atomizing inhalation of ribavirin and preparation method thereof
CN115463117A (en) Budesonide salbutamol compound aerosol inhalation suspension with high delivery efficiency and preparation method thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination