CN112057438A - Ribavirin solution for inhalation and preparation method and application thereof - Google Patents
Ribavirin solution for inhalation and preparation method and application thereof Download PDFInfo
- Publication number
- CN112057438A CN112057438A CN202010965337.1A CN202010965337A CN112057438A CN 112057438 A CN112057438 A CN 112057438A CN 202010965337 A CN202010965337 A CN 202010965337A CN 112057438 A CN112057438 A CN 112057438A
- Authority
- CN
- China
- Prior art keywords
- ribavirin
- solution
- benzalkonium chloride
- inhalation
- injection
- 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
Links
Classifications
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
-
- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/186—Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
-
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
Abstract
The invention is applicable to the technical field of medicaments, and provides a ribavirin solution for inhalation, a preparation method and application thereof, wherein each 3L of ribavirin solution comprises the following components: 40-80 g of ribavirin, 0.05-0.5 g of benzalkonium chloride and 0.3-0.9 g of edetate disodium. In addition, the preparation method of the ribavirin solution comprises the following steps: mixing benzalkonium chloride, disodium edetate and water for injection, and then adding ribavirin for mixing to obtain a mixed solution; filtering the mixed solution for the first time to obtain filtrate; and (3) adjusting the pH of the filtrate to 4.5-6.5 by using a pH regulator, adding water for injection to perform constant volume, and filtering for the second time to obtain the ribavirin solution. According to the invention, the ribavirin, the benzalkonium chloride and the disodium edetate are compounded for use, so that the solubility of the ribavirin in water can be promoted, and the absorption effect of the ribavirin can be improved.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a ribavirin solution for inhalation, and a preparation method and application thereof.
Background
Ribavirin is a nucleoside analog synthesized in 1972 and is known to have a wide range of antiviral activity against RNA and DNA viruses. The drug is a therapeutic drug for chronic hepatitis C, and is expected to be more effective than the administration of IFN alpha-2 b alone when interferon alpha-2 b (gene recombination) (hereinafter referred to as IFN alpha-2 b) is administered in combination with a patient suffering from chronic interfering hepatitis C. Approval was obtained in the united states in 1998 and in europe in 1999. In Japan, the combination administration of this drug with IFN α -2b (hereinafter referred to as IFN/R combination) was approved for chronic hepatitis C in 2001. In addition, 48 weeks of IFN/R administration was approved in 2004.
Dosage forms of traditional ribavirin drugs include the following: 1. aerosol: the propellant is tetrafluoroethane and suspension. 2. Injection liquid: the adjuvants are sodium chloride, medicinal charcoal, and injectable water; the effective period is 24 months. 3. Freeze-dried powder for inhalation: ribavirin is used in an inhalation solution as a sterile lyophilized powder that can be reconstituted for aerosol administration. Each 100mL glass vial contains 6 grams of ribavirin, which when formulated to the recommended volume of 300mL with sterile water for injection, USP, or sterile water for inhalation (without added preservatives) will contain 20mg of ribavirin per mL, at a pH of about 5.5; using only small particle aerosol generators (
-2) an atomizer.
Compared with the medicine in the form of injection, the medicine in the form of aerosol and freeze-dried powder for inhalation is more convenient to use and has higher safety. However, the ribavirin drugs of the traditional aerosol have the problems of poor drug absorption effect and the like, the ribavirin drugs of the traditional freeze-dried powder for inhalation need to be prepared newly for clinical use and can be used by professionals, and the risk in the aspect of medication safety is increased, so the existing ribavirin drugs need to be improved.
Disclosure of Invention
An object of an embodiment of the present invention is to provide a ribavirin solution for inhalation, which aims to solve the problems proposed in the background art.
The embodiment of the invention is realized by a ribavirin solution for inhalation, wherein each 3L of ribavirin solution comprises the following components: 40-80 g of ribavirin, 0.05-0.5 g of benzalkonium chloride and 0.3-0.9 g of edetate disodium.
As a preferred embodiment of the present invention, every 3L of the ribavirin solution comprises the following components: 50-70 g of ribavirin, 0.1-0.3 g of benzalkonium chloride and 0.5-0.7 g of edetate disodium.
As another preferred aspect of the present embodiment, the ribavirin solution further comprises a pH adjusting agent; the pH value of the ribavirin solution is 4.5-6.5.
Another object of an embodiment of the present invention is to provide a method for preparing a ribavirin solution, which comprises the following steps:
weighing ribavirin, benzalkonium chloride and disodium edetate according to the dosage of each component in 3L of ribavirin solution;
mixing benzalkonium chloride, disodium edetate and water for injection, and then adding ribavirin for mixing to obtain a mixed solution;
filtering the mixed solution for the first time to obtain filtrate;
and (3) adjusting the pH of the filtrate to 4.5-6.5 by using a pH regulator, adding water for injection to perform constant volume, and filtering for the second time to obtain the ribavirin solution.
In another preferable embodiment of the present invention, in the step, benzalkonium chloride, edetate disodium and water for injection are mixed at a temperature of 60 to 80 ℃.
As another preferable scheme of the embodiment of the invention, in the step, a polypropylene filter membrane with the pore diameter of 0.4-0.5 μm is adopted for primary filtration.
In another preferable scheme of the embodiment of the invention, in the step, a polyethersulfone filter membrane or a polyvinylidene fluoride filter membrane with the pore diameter of 0.2-0.25 μm is adopted for secondary filtration.
As another preferable mode of the embodiment of the present invention, the pH adjuster is hydrochloric acid or sodium hydroxide.
Another object of the embodiments of the present invention is to provide a ribavirin solution prepared by the above preparation method.
It is another object of an embodiment of the present invention to provide a use of the above ribavirin solution in the preparation of a medicament in the form of an inhalation formulation.
According to the ribavirin solution for inhalation provided by the embodiment of the invention, ribavirin, benzalkonium chloride and edetate disodium are compounded for use, so that the solubility of ribavirin in water can be promoted, and the absorption effect of ribavirin can be improved; compared with the traditional inhalation spray formulation, the SPAG-2 atomization treatment adopted by the ribavirin solution can take effect in local absorption, and the ribavirin solution is suitable for treating hospitalized infants with serious lower respiratory tract infection caused by RSV (respiratory syncytial virus), so that the ribavirin solution can be treated as soon as possible in the serious lower respiratory tract infection process and achieve better curative effect.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Example 1
This embodiment provides a ribavirin solution for inhalation, which is prepared by the method comprising the steps of:
s1, weighing 40g of ribavirin, 0.05g of benzalkonium chloride and 0.3g of edetate disodium for later use.
S2, adding the benzalkonium chloride and the edetate disodium into a beaker, adding 2.8L of sterile water for injection at 60 ℃ into the beaker, stirring and mixing until the benzalkonium chloride and the edetate disodium are completely dissolved, cooling the solution to room temperature, adding the weighed ribavirin, stirring and mixing until the ribavirin is dissolved, and obtaining a mixed solution.
S3, performing circulating filtration on the mixed solution at a flow rate of 100mL/min for 45min by using a positive pressure sieve filter, a polypropylene filter membrane with a pore diameter of 0.4 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain a filtrate.
S4, adding a proper amount of pH regulator into the filtrate to regulate the pH to 4.5, adding sterile water for injection to a constant volume of 3L, and performing circulating filtration on the solution with the constant volume for 45min at a flow rate of 100mL/min by using a positive pressure sieve filter, a polyether sulfone filter membrane with the pore diameter of 0.2 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain the ribavirin solution. Wherein, when the pH value is too high, the pH regulator can adopt hydrochloric acid for regulation; when the pH is too low, the pH adjuster may be adjusted with sodium hydroxide.
S5, subpackaging the ribavirin solution into 300mL glass bottles, wherein each glass bottle contains 300mL, and sealing.
Example 2
This embodiment provides a ribavirin solution for inhalation, which is prepared by the method comprising the steps of:
s1, weighing 80g of ribavirin, 0.5g of benzalkonium chloride and 0.9g of edetate disodium for later use.
S2, adding the benzalkonium chloride and the edetate disodium into a beaker, adding 2.8L of sterile water for injection at 80 ℃ into the beaker, stirring and mixing until the benzalkonium chloride and the edetate disodium are completely dissolved, cooling the solution to room temperature, adding the weighed ribavirin, stirring and mixing until the ribavirin is dissolved, and obtaining a mixed solution.
S3, performing circulating filtration on the mixed solution at a flow rate of 100mL/min for 45min by using a positive pressure sieve filter, a polypropylene filter membrane with a pore diameter of 0.5 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain a filtrate.
S4, adding a proper amount of pH regulator into the filtrate to regulate the pH to 6.5, adding sterile water for injection to a constant volume of 3L, and performing circulating filtration on the solution with the constant volume for 45min at a flow rate of 100mL/min by using a positive pressure sieve filter, a polyvinylidene fluoride filter membrane with the pore diameter of 0.25 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain the ribavirin solution. Wherein, when the pH value is too high, the pH regulator can adopt hydrochloric acid for regulation; when the pH is too low, the pH adjuster may be adjusted with sodium hydroxide.
S5, subpackaging the ribavirin solution into 300mL glass bottles, wherein each glass bottle contains 300mL, and sealing.
Example 3
This embodiment provides a ribavirin solution for inhalation, which is prepared by the method comprising the steps of:
s1, weighing 45g of ribavirin, 0.4g of benzalkonium chloride and 0.4g of edetate disodium for later use.
S2, adding the benzalkonium chloride and the edetate disodium into a beaker, adding 2.8L of sterile water for injection at 65 ℃ into the beaker, stirring and mixing until the benzalkonium chloride and the edetate disodium are completely dissolved, cooling the solution to room temperature, adding the weighed ribavirin, stirring and mixing until the ribavirin is dissolved, and obtaining a mixed solution.
S3, performing circulating filtration on the mixed solution at a flow rate of 100mL/min for 45min by using a positive pressure sieve filter, a polypropylene filter membrane with a pore diameter of 0.45 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain a filtrate.
S4, adding a proper amount of pH regulator into the filtrate to regulate the pH to 5, adding sterile water for injection to a constant volume of 3L, and performing circulating filtration on the solution with the constant volume for 45min at a flow rate of 100mL/min by using a positive pressure sieve filter, a polyvinylidene fluoride filter membrane with the pore diameter of 0.22 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain the ribavirin solution. Wherein, when the pH value is too high, the pH regulator can adopt hydrochloric acid for regulation; when the pH is too low, the pH adjuster may be adjusted with sodium hydroxide.
S5, subpackaging the ribavirin solution into 300mL glass bottles, wherein each glass bottle contains 300mL, and sealing.
Example 4
This embodiment provides a ribavirin solution for inhalation, which is prepared by the method comprising the steps of:
s1, weighing 75g of ribavirin, 0.08g of benzalkonium chloride and 0.8g of edetate disodium for later use.
S2, adding the benzalkonium chloride and the edetate disodium into a beaker, adding 2.8L of sterile water for injection at 75 ℃ into the beaker, stirring and mixing until the benzalkonium chloride and the edetate disodium are completely dissolved, cooling the solution to room temperature, adding the weighed ribavirin, stirring and mixing until the ribavirin is dissolved, and obtaining a mixed solution.
S3, performing circulating filtration on the mixed solution at a flow rate of 100mL/min for 45min by using a positive pressure sieve filter, a polypropylene filter membrane with a pore diameter of 0.45 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain a filtrate.
S4, adding a proper amount of pH regulator into the filtrate to regulate the pH to 6, adding sterile water for injection to a constant volume of 3L, and performing circulating filtration on the solution with the constant volume for 45min at a flow rate of 100mL/min by using a positive pressure sieve filter, a polyether sulfone filter membrane with the pore diameter of 0.22 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain the ribavirin solution. Wherein, when the pH value is too high, the pH regulator can adopt hydrochloric acid for regulation; when the pH is too low, the pH adjuster may be adjusted with sodium hydroxide.
S5, subpackaging the ribavirin solution into 300mL glass bottles, wherein each glass bottle contains 300mL, and sealing.
Example 5
This embodiment provides a ribavirin solution for inhalation, which is prepared by the method comprising the steps of:
s1, weighing 50g of ribavirin, 0.1g of benzalkonium chloride and 0.5g of edetate disodium for later use.
S2, adding the benzalkonium chloride and the edetate disodium into a beaker, adding 2.8L of sterile water for injection at 70 ℃ into the beaker, stirring and mixing until the benzalkonium chloride and the edetate disodium are completely dissolved, cooling the solution to room temperature, adding the weighed ribavirin, stirring and mixing until the ribavirin is dissolved, and obtaining a mixed solution.
S3, performing circulating filtration on the mixed solution at a flow rate of 100mL/min for 45min by using a positive pressure sieve filter, a polypropylene filter membrane with a pore diameter of 0.45 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain a filtrate.
S4, adding a proper amount of pH regulator into the filtrate to regulate the pH to 5.5, adding sterile water for injection to a constant volume of 3L, and performing circulating filtration on the solution with the constant volume for 45min at a flow rate of 100mL/min by using a positive pressure sieve filter, a polyether sulfone filter membrane with the pore diameter of 0.22 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain the ribavirin solution. Wherein, when the pH value is too high, the pH regulator can adopt hydrochloric acid for regulation; when the pH is too low, the pH adjuster may be adjusted with sodium hydroxide.
S5, subpackaging the ribavirin solution into 300mL glass bottles, wherein each glass bottle contains 300mL, and sealing.
Example 6
This embodiment provides a ribavirin solution for inhalation, which is prepared by the method comprising the steps of:
s1, weighing 70g of ribavirin, 0.3g of benzalkonium chloride and 0.7g of edetate disodium for later use.
S2, adding the benzalkonium chloride and the edetate disodium into a beaker, adding 2.8L of sterile water for injection at 70 ℃ into the beaker, stirring and mixing until the benzalkonium chloride and the edetate disodium are completely dissolved, cooling the solution to room temperature, adding the weighed ribavirin, stirring and mixing until the ribavirin is dissolved, and obtaining a mixed solution.
S3, performing circulating filtration on the mixed solution at a flow rate of 100mL/min for 45min by using a positive pressure sieve filter, a polypropylene filter membrane with a pore diameter of 0.45 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain a filtrate.
S4, adding a proper amount of pH regulator into the filtrate to regulate the pH to 5.5, adding sterile water for injection to a constant volume of 3L, and performing circulating filtration on the solution with the constant volume for 45min at a flow rate of 100mL/min by using a positive pressure sieve filter, a polyether sulfone filter membrane with the pore diameter of 0.22 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain the ribavirin solution. Wherein, when the pH value is too high, the pH regulator can adopt hydrochloric acid for regulation; when the pH is too low, the pH adjuster may be adjusted with sodium hydroxide.
S5, subpackaging the ribavirin solution into 300mL glass bottles, wherein each glass bottle contains 300mL, and sealing.
Example 7
This embodiment provides a ribavirin solution for inhalation, which is prepared by the method comprising the steps of:
s1, weighing 60g of ribavirin, 0.1g of benzalkonium chloride and 0.7g of edetate disodium for later use.
S2, adding the benzalkonium chloride and the edetate disodium into a beaker, adding 2.8L of sterile water for injection at 70 ℃ into the beaker, stirring and mixing until the benzalkonium chloride and the edetate disodium are completely dissolved, cooling the solution to room temperature, adding the weighed ribavirin, stirring and mixing until the ribavirin is dissolved, and obtaining a mixed solution.
S3, performing circulating filtration on the mixed solution at a flow rate of 100mL/min for 45min by using a positive pressure sieve filter, a polypropylene filter membrane with a pore diameter of 0.45 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain a filtrate.
S4, adding a proper amount of pH regulator into the filtrate to regulate the pH to 5.5, adding sterile water for injection to a constant volume of 3L, and performing circulating filtration on the solution with the constant volume for 45min at a flow rate of 100mL/min by using a positive pressure sieve filter, a polyether sulfone filter membrane with the pore diameter of 0.22 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain the ribavirin solution. Wherein, when the pH value is too high, the pH regulator can adopt hydrochloric acid for regulation; when the pH is too low, the pH adjuster may be adjusted with sodium hydroxide.
S5, subpackaging the ribavirin solution into 300mL glass bottles, wherein each glass bottle contains 300mL, and sealing.
Example 8
This embodiment provides a ribavirin solution for inhalation, which is prepared by the method comprising the steps of:
s1, weighing 60g of ribavirin, 0.3g of benzalkonium chloride and 0.5g of edetate disodium for later use.
S2, adding the benzalkonium chloride and the edetate disodium into a beaker, adding 2.8L of sterile water for injection at 70 ℃ into the beaker, stirring and mixing until the benzalkonium chloride and the edetate disodium are completely dissolved, cooling the solution to room temperature, adding the weighed ribavirin, stirring and mixing until the ribavirin is dissolved, and obtaining a mixed solution.
S3, performing circulating filtration on the mixed solution at a flow rate of 100mL/min for 45min by using a positive pressure sieve filter, a polypropylene filter membrane with a pore diameter of 0.45 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain a filtrate.
S4, adding a proper amount of pH regulator into the filtrate to regulate the pH to 5.5, adding sterile water for injection to a constant volume of 3L, and performing circulating filtration on the solution with the constant volume for 45min at a flow rate of 100mL/min by using a positive pressure sieve filter, a polyether sulfone filter membrane with the pore diameter of 0.22 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain the ribavirin solution. Wherein, when the pH value is too high, the pH regulator can adopt hydrochloric acid for regulation; when the pH is too low, the pH adjuster may be adjusted with sodium hydroxide.
S5, subpackaging the ribavirin solution into 300mL glass bottles, wherein each glass bottle contains 300mL, and sealing.
Example 9
This embodiment provides a ribavirin solution for inhalation, which is prepared by the method comprising the steps of:
s1, weighing 60g of ribavirin, 0.2g of benzalkonium chloride and 0.6g of edetate disodium for later use.
S2, adding the benzalkonium chloride and the edetate disodium into a beaker, adding 2.8L of sterile water for injection at 70 ℃ into the beaker, stirring and mixing until the benzalkonium chloride and the edetate disodium are completely dissolved, cooling the solution to room temperature, adding the weighed ribavirin, stirring and mixing until the ribavirin is dissolved, and obtaining a mixed solution.
S3, performing circulating filtration on the mixed solution at a flow rate of 100mL/min for 45min by using a positive pressure sieve filter, a polypropylene filter membrane with a pore diameter of 0.45 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain a filtrate.
S4, adding a proper amount of pH regulator into the filtrate to regulate the pH to 5.5, adding sterile water for injection to a constant volume of 3L, and performing circulating filtration on the solution with the constant volume for 45min at a flow rate of 100mL/min by using a positive pressure sieve filter, a polyether sulfone filter membrane with the pore diameter of 0.22 mu m, a peristaltic pump and a No. 15 peristaltic pump tube to obtain the ribavirin solution. Wherein, when the pH value is too high, the pH regulator can adopt hydrochloric acid for regulation; when the pH is too low, the pH adjuster may be adjusted with sodium hydroxide.
S5, subpackaging the ribavirin solution into 300mL glass bottles, wherein each glass bottle contains 300mL, and sealing.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (10)
1. A ribavirin solution for inhalation comprising the following composition for every 3L of said ribavirin solution: 40-80 g of ribavirin, 0.05-0.5 g of benzalkonium chloride and 0.3-0.9 g of edetate disodium.
2. A ribavirin solution for inhalation according to claim 1, wherein every 3L of said ribavirin solution comprises the following components: 50-70 g of ribavirin, 0.1-0.3 g of benzalkonium chloride and 0.5-0.7 g of edetate disodium.
3. A ribavirin solution for inhalation according to claim 1 or 2, characterized in that it further comprises a pH adjusting agent; the pH value of the ribavirin solution is 4.5-6.5.
4. A process for the preparation of a ribavirin solution as claimed in any one of claims 1 to 3 which comprises the steps of:
weighing ribavirin, benzalkonium chloride and disodium edetate according to the dosage of each component in 3L of ribavirin solution;
mixing benzalkonium chloride, disodium edetate and water for injection, and then adding ribavirin for mixing to obtain a mixed solution;
filtering the mixed solution for the first time to obtain filtrate;
and (3) adjusting the pH of the filtrate to 4.5-6.5 by using a pH regulator, adding water for injection to perform constant volume, and filtering for the second time to obtain the ribavirin solution.
5. The method for preparing ribavirin solution for inhalation according to claim 4, wherein in the step, benzalkonium chloride, disodium edetate and water for injection are mixed at a temperature of 60-80 ℃.
6. The method for preparing ribavirin solution for inhalation according to claim 4, wherein in the step, polypropylene filter membranes with the pore diameter of 0.4-0.5 μm are used for primary filtration.
7. The method for preparing ribavirin solution for inhalation according to claim 4, wherein in the step, the secondary filtration is performed by using a polyethersulfone filter membrane or a polyvinylidene fluoride filter membrane with the pore size of 0.2-0.25 μm.
8. The method for preparing ribavirin solution for inhalation according to claim 4, wherein the pH adjusting agent is hydrochloric acid or sodium hydroxide.
9. A ribavirin solution prepared by the preparation method as claimed in any one of claims 4 to 8.
10. Use of a ribavirin solution as claimed in any one of claims 1 to 3 and claim 9 in the manufacture of a medicament for inhalation dosage form.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010965337.1A CN112057438A (en) | 2020-09-15 | 2020-09-15 | Ribavirin solution for inhalation and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010965337.1A CN112057438A (en) | 2020-09-15 | 2020-09-15 | Ribavirin solution for inhalation and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112057438A true CN112057438A (en) | 2020-12-11 |
Family
ID=73696764
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010965337.1A Pending CN112057438A (en) | 2020-09-15 | 2020-09-15 | Ribavirin solution for inhalation and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112057438A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1385165A (en) * | 2002-06-05 | 2002-12-18 | 李大鹏 | Ribavirin aerosol inhalation solution |
| CN111228244A (en) * | 2020-03-27 | 2020-06-05 | 杭州汉库医药科技有限公司 | Ribavirin inhalation preparation and application thereof in preparation of medicine for treating neocoronary pneumonia |
| CN111297838A (en) * | 2020-04-08 | 2020-06-19 | 宁波合康生物医药科技有限公司 | Inhalation spray of antiviral drug |
-
2020
- 2020-09-15 CN CN202010965337.1A patent/CN112057438A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1385165A (en) * | 2002-06-05 | 2002-12-18 | 李大鹏 | Ribavirin aerosol inhalation solution |
| CN111228244A (en) * | 2020-03-27 | 2020-06-05 | 杭州汉库医药科技有限公司 | Ribavirin inhalation preparation and application thereof in preparation of medicine for treating neocoronary pneumonia |
| CN111297838A (en) * | 2020-04-08 | 2020-06-19 | 宁波合康生物医药科技有限公司 | Inhalation spray of antiviral drug |
Non-Patent Citations (1)
| Title |
|---|
| 裘雪友主编, 北京人民军医出版社 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1293916C (en) | Stable insulin formulations | |
| JP2004532262A5 (en) | ||
| CN107789340A (en) | A kind of Herba Andrographitis Neulized inhalation pharmaceutical solutions and preparation method thereof | |
| EP2127659A1 (en) | Use of high osmotic liquid composition in manufacturing medicament for enhancing wound healing | |
| KR101330394B1 (en) | Medical solution, method for producing and use thereof | |
| KR20140025314A (en) | A combination composition | |
| CN105311081A (en) | Application of Shanhaidan chrysanthemum indicum injection in aerosol inhalation, spray bottle aerial fog and rectal administration and method | |
| CN112057438A (en) | Ribavirin solution for inhalation and preparation method and application thereof | |
| US7470666B2 (en) | Use of Ulinastatin and its pharmaceutical composition for treating severe acute respiratory syndrome | |
| CN113368208A (en) | Antiviral aerosol inhalation solution preparation and preparation method thereof | |
| CN113797318A (en) | Interferon composition, and preparation method and application thereof | |
| TWI291874B (en) | ||
| KR0156929B1 (en) | Stabilized water-soluble solution of pentamidine and its salts | |
| CN104688670A (en) | Invokana sustained release preparation and preparation method thereof | |
| CN112999204A (en) | Shuanghuanglian aerosol inhalation solution preparation and preparation method thereof | |
| KR20060002795A (en) | Compositions and methods for preventing and treating endotoxin-related diseases and conditions | |
| CN115607508B (en) | Nasal administration preparation for preventing and treating pneumonia caused by influenza A virus and preparation method and application thereof | |
| CN102380088A (en) | Prescription and preparation method of thymopeptide-5 injection | |
| CN107137518A (en) | A kind of 'Zhichuanling Neulized inhalation pharmaceutical solutions and preparation method thereof | |
| CN101019872B (en) | Nanometer antiviral liposome medicine and its preparation | |
| Carr et al. | Gentamicin dosing requirements in patients with acute pancreatitis | |
| JPS5938207B2 (en) | Kidney disease treatment | |
| JP3655645B2 (en) | Transmucosal agent | |
| CN107773581A (en) | A kind of silver yellow Neulized inhalation pharmaceutical solutions and preparation method thereof | |
| CN114948914B (en) | Moxifloxacin hydrochloride solution for aerosol inhalation 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 |