CN114557961A - Slow-release enrofloxacin suspension and preparation method thereof - Google Patents

Slow-release enrofloxacin suspension and preparation method thereof Download PDF

Info

Publication number
CN114557961A
CN114557961A CN202210147063.4A CN202210147063A CN114557961A CN 114557961 A CN114557961 A CN 114557961A CN 202210147063 A CN202210147063 A CN 202210147063A CN 114557961 A CN114557961 A CN 114557961A
Authority
CN
China
Prior art keywords
enrofloxacin
percent
slow
release
suspension
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
CN202210147063.4A
Other languages
Chinese (zh)
Inventor
李江
王榆鑫
曾月
赵素梅
韩雯静
陈静月
谭宜菊
张伟
舒刚
符华林
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.)
Sichuan Yongnuo Biotechnology Co ltd
Original Assignee
Sichuan Yongnuo Biotechnology 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 Sichuan Yongnuo Biotechnology Co ltd filed Critical Sichuan Yongnuo Biotechnology Co ltd
Priority to CN202210147063.4A priority Critical patent/CN114557961A/en
Publication of CN114557961A publication Critical patent/CN114557961A/en
Pending legal-status Critical Current

Links

Images

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
    • A61K9/10—Dispersions; Emulsions
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • 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
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Engineering & Computer Science (AREA)
  • Communicable Diseases (AREA)
  • Dispersion Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Oncology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention discloses a slow-release enrofloxacin suspension and a preparation method thereof, wherein the slow-release enrofloxacin suspension comprises the following components in percentage by mass: 3 to 8 percent of enrofloxacin, 0.8 to 1.0 percent of methylcellulose, 10 to 15 percent of glycerol, 0.8 to 1.2 percent of citric acid, 0.02 to 0.10 percent of sodium benzoate and the balance of purified water, wherein the total mass percentage is 100 percent. The suspension is prepared by adopting a fine crystallization mode, so that the enrofloxacin is dispersed in a colloidal solution of the suspending agent in a superfine microcrystalline form, the stability of the suspension is obviously improved, the glycerol is used as a sweetening agent, the palatability of the product is improved, the absorption is good, the acting time is long, the preparation method is simple, the bioavailability of the enrofloxacin can be improved, and the product can play a more efficient role.

Description

Slow-release enrofloxacin suspension and preparation method thereof
Technical Field
The invention belongs to the technical field of veterinary medicines, and particularly relates to a slow-release enrofloxacin suspension and a preparation method thereof.
Background
The fluoroquinolone medicines are more and more widely applied in veterinary clinical application in China, but the development and research of the preparation are laggard, most of the fluoroquinolone medicines are common preparations such as injection, powder, oral solution, a few ointments and the like at present, and no long-acting preparation is reported. Enrofloxacin liposome, oral sustained release agent and drenching agent have been reported abroad. The common preparation of fluoroquinolone medicaments for animals needs to be administered for 2 times in 1 day, particularly injections, and frequent administration not only consumes labor and time, but also causes stress reaction of animals. In order to delay drug absorption and prolong the effective blood concentration maintaining time, thereby reducing the administration frequency, a new dosage form is urgently needed to make up the defects of the existing dosage form. The suspension is a non-uniform liquid preparation formed by dispersing the drug in a medium in a particulate state, and after part of the dissolved drug and small-particle drug in the suspension enter an animal body, the blood drug peak concentration can be reached in a short time, so that the drug effect can be quickly exerted; the slow release part is a drug suspension particle, and has the effect of maintaining the effective drug concentration for a long time due to slow release.
Enrofloxacin, also known as ethyl ciprofloxacin, is a third-generation quinolone antibacterial drug special for animals, has an action mechanism that antibacterial effect is achieved by inhibiting bacterial DNA helicase, and the metabolism in animals is mainly to remove ethyl to become ciprofloxacin. Enrofloxacin is a spectrum bactericidal drug, has bactericidal effects on mycoplasma, escherichia coli, klebsiella, salmonella, proteus, pseudomonas aeruginosa, haemophilus, pasteurella multocida, haemolytic pasteurella, staphylococcus aureus, streptococcus and the like, has the advantages of wide bactericidal spectrum, wide in-vivo distribution, no cross drug resistance with other drugs and the like, and is mainly used for preventing and treating animal bacterial infection and mycoplasma infectious diseases in veterinary clinic. Because enrofloxacin has poor water solubility, bitter taste, large irritation and easy decomposition, the application in veterinary clinic is greatly limited, at present, commonly used enrofloxacin preparations mainly comprise emulsion, solid granules, injection and the like, and common injection has short half-life, quick elimination in vivo, needs to be administered for multiple times, wastes time and labor; the emulsion has low drug content and needs to be administrated for a plurality of times; the solid granules have low bioavailability and are not beneficial to large-scale administration. Because enrofloxacin is bitter in taste, the oral solution and soluble powder on the market are both used on chickens at present, and the application on pigs is less.
Therefore, a new slow-release enrofloxacin suspension needs to be provided.
Disclosure of Invention
In view of the above, the invention provides a slow-release enrofloxacin suspension and a preparation method thereof, aiming at the problem of poor solubility of enrofloxacin.
In order to solve the technical problems, the invention discloses a slow-release enrofloxacin suspension which comprises the following components in percentage by mass: 3 to 8 percent of enrofloxacin, 0.8 to 1.0 percent of methylcellulose, 10 to 15 percent of glycerol, 0.8 to 1.2 percent of citric acid, 0.02 to 0.10 percent of sodium benzoate and the balance of purified water, wherein the total mass percentage is 100 percent.
The invention discloses a preparation method of a slow-release enrofloxacin suspension, which comprises the following steps:
step 1, weighing the following components in percentage by mass: 3 to 8 percent of enrofloxacin, 0.8 to 1.0 percent of methylcellulose, 10 to 15 percent of glycerol, 0.8 to 1.2 percent of citric acid, 0.02 to 0.10 percent of sodium benzoate and the balance of purified water, wherein the total mass percentage is 100 percent;
step 2, swelling methyl cellulose;
step 3, carrying out dispersion treatment on the enrofloxacin;
step 4, adding 5 drops of sodium hydroxide solution into the dispersed enrofloxacin to dissolve the enrofloxacin, adding weighed citric acid, uniformly stirring, sequentially adding the swelled methylcellulose, glycerol and sodium benzoate while stirring, stirring and mixing, finally adding purified water to a constant volume to prepare a liquid medicine, and performing all operations at room temperature; stirring the prepared liquid medicine and homogenizing;
and 5, canning, sealing and sterilizing to prepare the slow-release enrofloxacin suspension.
Optionally, the glassware used in this method may need to be subjected to the following treatments prior to use: the glass metering instrument should be drained naturally and not baked in an oven; pushing the rest glass instruments into an upper plate of a washing machine, starting the washing machine, putting the glass instruments into an oven for drying after ultrasonic cleaning and purified water rinsing, and sterilizing according to a specified sterilization program; the pressure of the purified water for washing is more than or equal to 0.2 Mpa; the speed of the motor of the washing machine is not more than 50 Hz; the temperature in the sterilization stage was 180 ℃ and the sterilization time was 1.5 hours.
Optionally, the swelling treatment of the methylcellulose in the step 2 is specifically performed according to the following steps: putting the weighed methylcellulose into a beaker, adding purified water accounting for 30 percent of the total volume of the slow-release enrofloxacin suspension, stirring for 3-4h on a magnetic stirrer, and swelling for later use.
Optionally, the dispersion treatment of enrofloxacin in step 3 specifically comprises: grinding the weighed enrofloxacin for 10-20min, grinding, and adding purified water for dispersion.
Optionally, the concentration of the sodium hydroxide solution in the step 4 is 2 mol/L.
Optionally, the stirring and mixing time in the step 4 is 25-35 min.
Optionally, the homogenizing the prepared liquid medicine while stirring in the step 4 specifically includes: homogenizing at 300-500 bar for 2 times, and regulating pressure to 1600bar for 8 times.
Optionally, the sterilization pressure in step 5 is 0.3-0.6Mpa, the sterilization temperature is 115 ℃, and the time duration is 30 min.
Compared with the prior art, the invention can obtain the following technical effects:
the suspension is prepared by adopting a fine crystallization mode, so that the enrofloxacin is dispersed in a colloidal solution of the suspending agent in a superfine microcrystalline form, the stability of the suspension is obviously improved, the glycerol is used as a sweetening agent, the palatability of the product is improved, the absorption is good, the acting time is long, the preparation method is simple, the bioavailability of the enrofloxacin can be improved, and the product can play a more efficient role.
Of course, it is not necessary for any product to achieve all of the above-described technical effects simultaneously in the practice of the invention.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention and not to limit the invention. In the drawings:
FIG. 1 is a box-packed diagram of a sustained release enrofloxacin suspension of the present invention;
FIG. 2 is a bottled picture of the slow release enrofloxacin suspension.
Detailed Description
The following embodiments are described in detail with reference to the accompanying drawings, so that how to implement the technical features of the present invention to solve the technical problems and achieve the technical effects can be fully understood and implemented.
The invention provides a slow-release enrofloxacin suspension which comprises the following components in percentage by mass: 3 to 8 percent of enrofloxacin, 0.8 to 1.0 percent of methylcellulose, 10 to 15 percent of glycerol, 0.8 to 1.2 percent of citric acid, 0.02 to 0.10 percent of sodium benzoate and the balance of purified water, wherein the total mass percentage is 100 percent.
The appearance of the slow-release enrofloxacin suspension prepared by the invention is shown in figure 1 and figure 2.
The invention also discloses a preparation method of the slow-release enrofloxacin suspension, which comprises the following steps:
step 1, weighing the following components in percentage by mass: 3 to 8 percent of enrofloxacin, 0.8 to 1.0 percent of methylcellulose, 10 to 15 percent of glycerol, 0.8 to 1.2 percent of citric acid, 0.02 to 0.10 percent of sodium benzoate and the balance of purified water, wherein the total mass percentage is 100 percent;
and 2, swelling the methyl cellulose: putting the weighed methylcellulose into a beaker, adding purified water accounting for 30 percent of the total volume of the slow-release enrofloxacin suspension, stirring for 3-4h on a magnetic stirrer, and swelling for later use;
step 3, carrying out dispersion treatment on the enrofloxacin: grinding the weighed enrofloxacin for 10-20min, grinding, and adding a proper amount of purified water for dispersion;
step 4, adding 5 drops of 2mol/L sodium hydroxide solution into the dispersed enrofloxacin to dissolve the enrofloxacin, adding weighed citric acid, uniformly stirring, sequentially adding the swelled methylcellulose, glycerol and sodium benzoate while stirring, stirring and mixing for 25-35min, finally adding purified water to a constant volume, and performing all the operations at room temperature; homogenizing the prepared medicinal liquid with homogenizer at 300-500 bar for 2 times, and homogenizing under pressure of 1600bar for 8 times while stirring.
And 5, canning, sealing and sterilizing, wherein the sterilization pressure is 0.3-0.6Mpa, the sterilization temperature is 115 ℃, and the time duration is 30min, so as to prepare the slow-release enrofloxacin suspension.
The glassware used in this method needs to be subjected to the following treatments before use: the glass metering instrument should be drained naturally and not baked in an oven; pushing the rest glass instruments into an upper plate of a washing machine, starting the washing machine, putting the glass instruments into an oven for drying after ultrasonic cleaning and purified water rinsing, and sterilizing according to a specified sterilization program; the pressure of the purified water for washing is more than or equal to 0.2 Mpa; the speed of the motor of the washing machine is not more than 50 Hz; the temperature in the sterilization stage was 180 ℃ and the sterilization time was 1.5 hours.
Example 1
The slow-release enrofloxacin suspension comprises the following components in percentage by mass: 5% of enrofloxacin, 0.85% of methylcellulose, 14% of glycerin, 0.8% of citric acid, 0.06% of sodium benzoate and the balance of water, wherein the total mass percentage is 100%.
The preparation method of the slow-release enrofloxacin suspension comprises the following steps:
step 1, weighing the components according to the mass percentage;
and 2, swelling the methyl cellulose: putting the weighed methylcellulose into a beaker, adding purified water accounting for 30 percent of the total volume of the slow-release enrofloxacin suspension, stirring for 3.5 hours on a magnetic stirrer, and swelling for later use;
step 3, carrying out dispersion treatment on the enrofloxacin: grinding the weighed enrofloxacin for 15min, grinding, and adding a proper amount of purified water for dispersion;
step 4, adding 5 drops of 2mol/L sodium hydroxide solution into the dispersed enrofloxacin to dissolve the enrofloxacin, adding weighed citric acid, uniformly stirring, sequentially adding the swelled methylcellulose, glycerol and sodium benzoate while stirring, stirring and mixing for 30min, finally adding purified water to fix the volume, and performing all the operations at room temperature; homogenizing the prepared medicinal liquid with homogenizer at 400bar for 2 times, regulating pressure to 1600bar for 8 times, and stirring while homogenizing.
And 5, canning, sealing and sterilizing at the sterilization pressure of 0.45Mpa and the sterilization temperature of 115 ℃ for 30min to prepare the slow-release enrofloxacin suspension.
The glassware used in this method needs to be subjected to the following treatments before use: the glass metering instrument should be drained naturally and not baked in an oven; pushing the rest glass instruments into an upper plate of a washing machine, starting the washing machine, placing the glass instruments into an oven for drying after ultrasonic cleaning and purified water washing, and sterilizing according to a specified sterilization program; the pressure of the purified water for washing is more than or equal to 0.2 Mpa; the speed of the motor of the washing machine is not more than 50 Hz; the temperature in the sterilization stage was 180 ℃ and the sterilization time was 1.5 hours.
Example 2
The slow-release enrofloxacin suspension comprises the following components in percentage by mass: 3% of enrofloxacin, 0.8% of methylcellulose, 15% of glycerol, 0.8% of citric acid, 0.10% of sodium benzoate and the balance of purified water, wherein the total mass percentage is 100%.
The preparation method of the slow-release enrofloxacin suspension comprises the following steps:
step 1, weighing the components according to the mass percentage;
and 2, swelling the methyl cellulose: putting the weighed methylcellulose into a beaker, adding purified water accounting for 30 percent of the total volume of the slow-release enrofloxacin suspension, stirring for 3 hours on a magnetic stirrer, and swelling for later use;
step 3, carrying out dispersion treatment on the enrofloxacin: grinding weighed enrofloxacin for 20min, grinding, and adding a proper amount of purified water for dispersion;
step 4, adding 5 drops of 2mol/L sodium hydroxide solution into the dispersed enrofloxacin to dissolve the enrofloxacin, adding weighed citric acid, uniformly stirring, sequentially adding the swelled methylcellulose, glycerol and sodium benzoate while stirring, stirring and mixing for 25min, finally adding purified water to a constant volume, and performing all the operations at room temperature; homogenizing the prepared medicinal liquid with homogenizer at 500bar for 2 times, regulating pressure to 1600bar for 8 times, and stirring while homogenizing.
And 5, canning, sealing and sterilizing at the sterilization pressure of 0.3Mpa and the sterilization temperature of 115 ℃ for 30min to prepare the slow-release enrofloxacin suspension.
The glassware used in this method needs to be subjected to the following treatments before use: the metering glass should drain naturally and not bake in an oven; pushing the rest glass instruments into an upper plate of a washing machine, starting the washing machine, placing the glass instruments into an oven for drying after ultrasonic cleaning and purified water washing, and sterilizing according to a specified sterilization program; the pressure of the purified water for washing is more than or equal to 0.2 Mpa; the speed of the motor of the washing machine is not more than 50 Hz; the temperature in the sterilization stage was 180 ℃ and the sterilization time was 1.5 hours.
Example 3
The slow-release enrofloxacin suspension comprises the following components in percentage by mass: 8% of enrofloxacin, 1.0% of methylcellulose, 10% of glycerol, 1.2% of citric acid, 0.02% of sodium benzoate and the balance of purified water, wherein the total mass percentage is 100%.
The preparation method of the slow-release enrofloxacin suspension comprises the following steps:
step 1, weighing the components according to the mass percentage;
and 2, swelling the methyl cellulose: putting the weighed methylcellulose into a beaker, adding purified water accounting for 30 percent of the total volume of the slow-release enrofloxacin suspension, stirring for 4 hours on a magnetic stirrer, and swelling for later use;
step 3, carrying out dispersion treatment on the enrofloxacin: grinding the weighed enrofloxacin for 10min, grinding, and adding a proper amount of purified water for dispersion;
step 4, adding 5 drops of 2mol/L sodium hydroxide solution into the dispersed enrofloxacin to dissolve the enrofloxacin, adding weighed citric acid, uniformly stirring, sequentially adding the swelled methylcellulose, glycerol and sodium benzoate while stirring, stirring and mixing for 35min, finally adding purified water to fix the volume, and performing all the operations at room temperature; homogenizing the prepared liquid medicine with homogenizer at 300bar for 2 times, regulating pressure to 1600bar for 8 times, and stirring.
And 5, canning, sealing and sterilizing, wherein the sterilization pressure is 0.3-0.6Mpa, the sterilization temperature is 115 ℃, and the time duration is 30min, so as to prepare the slow-release enrofloxacin suspension.
The glassware used in this method needs to be subjected to the following treatments before use: the glass metering instrument should be drained naturally and not baked in an oven; pushing the rest glass instruments into an upper plate of a washing machine, starting the washing machine, placing the glass instruments into an oven for drying after ultrasonic cleaning and purified water washing, and sterilizing according to a specified sterilization program; the pressure of the purified water for washing is more than or equal to 0.2 Mpa; the speed of the motor of the washing machine is not more than 50 Hz; the temperature in the sterilization stage was 180 ℃ and the sterilization time was 1.5 hours.
Example 4
The slow-release enrofloxacin suspension comprises the following components in percentage by mass: 4% of enrofloxacin, 0.9% of methyl cellulose, 14% of glycerol, 1% of citric acid, 0.04% of sodium benzoate and the balance of purified water, wherein the total mass percentage content is 100%.
The preparation method of the slow-release enrofloxacin suspension is the same as that of the example 1.
Example 5
The slow-release enrofloxacin suspension comprises the following components in percentage by mass: 6 percent of enrofloxacin, 0.95 percent of methylcellulose, 12 percent of glycerin, 0.9 percent of citric acid, 0.08 percent of sodium benzoate and the balance of purified water, wherein the total mass percentage is 100 percent.
The preparation method of the slow-release enrofloxacin suspension is the same as the example 1.
Comparative example 1
The slow-release enrofloxacin suspension comprises the following components in percentage by mass: 5% of enrofloxacin, 14% of glycerol, 0.8% of citric acid, 0.06% of sodium benzoate and the balance of water, wherein the total mass percentage content is 100%.
The preparation method of the slow-release enrofloxacin suspension is the same as the example 1.
Comparative example 2
The slow-release enrofloxacin suspension comprises the following components in percentage by mass: 5% of enrofloxacin, 0.85% of methylcellulose, 0.8% of citric acid, 0.06% of sodium benzoate and the balance of water, wherein the total mass percentage is 100%.
The preparation method of the slow-release enrofloxacin suspension is the same as the example 1.
Comparative example 3
The slow-release enrofloxacin suspension comprises the following components in percentage by mass: 5% of enrofloxacin, 0.85% of methylcellulose, 14% of glycerol and the balance of water, wherein the total mass percentage is 100%.
The preparation method of the slow-release enrofloxacin suspension is the same as the example 1.
The invention refers to 'pharmacopoeia of the people's republic of China ', pharmacopoeia of the animals of the people's republic of China 'and pharmacy' in 2020 edition, and performs quality evaluation on the prepared suspension, including character characteristics, sedimentation volume ratio, weight dispersity and the like, and adopts an ultraviolet-visible spectrophotometry to detect the content of enrofloxacin in the suspension, thereby laying a foundation for developing a new veterinary dosage form of enrofloxacin.
1. And (3) quality evaluation:
1.1, physical properties: the color, state and state of separation of the suspension were observed, and the pH value was measured with a pH meter.
1.2 determination of sedimentation volume ratio
Sedimentation volume ratio refers to the ratio of the volume of sediment to the volume of suspension before sedimentation. The measuring method comprises the following steps: 50mL of the product is taken and placed in a stoppered measuring cylinder, the cylinder is sealed, the cylinder is vigorously shaken for 1min, the height H0 of the beginning of the suspension is recorded, the cylinder is kept stand for 3H, and the final height H of the suspension is recorded.
Calculated as follows: sedimentation volume ratio of H/H0。
1.3 measurement of redispersibility
50mL of the enrofloxacin suspension was placed in a 50mL measuring cylinder, and allowed to settle. And (4) sealing the plug, after 24 hours, turning over the measuring cylinder after the measuring cylinder is turned over again (once the measuring cylinder is turned over, the force is uniformly applied during turning over), turning over the measuring cylinder for 3 times uniformly and forcibly, and observing whether the sediment at the bottom of the measuring cylinder disappears.
1.4, determination of drug content
(1) Drawing of standard curve
Reference methods were performed (Strongylofloxacin suspension and its preparation method: CN200510011669.1[ P ]). Accurately weighing 10mg of enrofloxacin reference substance dried to constant weight, placing the enrofloxacin reference substance in a 100mL volumetric flask, diluting the enrofloxacin reference substance to a scale by using 0.1mol/L hydrochloric acid solution to prepare stock solutions, respectively and accurately taking a proper amount of the stock solutions, placing the stock solutions in the 100mL volumetric flask, diluting the stock solutions to the scale by using 0.1mol/L hydrochloric acid solution to prepare 2, 3, 4, 5, 7, 9 and 10ug/mL standard solutions, measuring the absorbance at a position with a wavelength of 271nm, and regressing the value of the absorbance A to the value of the concentration C to obtain a regression equation.
(2) Determination of drug content
Randomly drawing 3 enrofloxacin suspension samples, respectively refining 1mL suspension samples, diluting the suspension samples with 0.1mol/L hydrochloric acid solution to obtain solution with enrofloxacin concentration of 5mg/mL, taking 0.1mol/L hydrochloric acid as blank control, measuring the absorbance of the diluted sample supernatant at the wavelength of 271nm, and calculating the enrofloxacin content in the samples by a regression equation.
Property indexes of slow-release enrofloxacin suspension prepared in examples 1-5 and comparative examples 1-5
TABLE 1 Property index of slow-release enrofloxacin suspension prepared in examples 1-5 and comparative examples 1-3
Figure BDA0003508693060000091
Figure BDA0003508693060000101
Figure BDA0003508693060000111
As can be seen from Table 1, the suspensions prepared in the examples have better content than the comparative examples, more uniform suspension degree and better mouthfeel.
While the foregoing description shows and describes several preferred embodiments of the invention, it is to be understood, as noted above, that the invention is not limited to the forms disclosed herein, but is not to be construed as excluding other embodiments and is capable of use in various other combinations, modifications, and environments and is capable of changes within the scope of the inventive concept as expressed herein, commensurate with the above teachings, or the skill or knowledge of the relevant art. And that modifications and variations may be effected by those skilled in the art without departing from the spirit and scope of the invention as defined by the appended claims.

Claims (9)

1. The slow-release enrofloxacin suspension is characterized by comprising the following components in percentage by mass: 3 to 8 percent of enrofloxacin, 0.8 to 1.0 percent of methylcellulose, 10 to 15 percent of glycerol, 0.8 to 1.2 percent of citric acid, 0.02 to 0.10 percent of sodium benzoate and the balance of purified water, wherein the total mass percentage is 100 percent.
2. A preparation method of slow-release enrofloxacin suspension is characterized by comprising the following steps:
step 1, weighing the following components in percentage by mass: 3 to 8 percent of enrofloxacin, 0.8 to 1.0 percent of methylcellulose, 10 to 15 percent of glycerol, 0.8 to 1.2 percent of citric acid, 0.02 to 0.10 percent of sodium benzoate and the balance of purified water, wherein the total mass percentage is 100 percent;
step 2, swelling methyl cellulose;
step 3, carrying out dispersion treatment on the enrofloxacin;
step 4, adding 5 drops of sodium hydroxide solution into the dispersed enrofloxacin to dissolve the enrofloxacin, adding weighed citric acid, uniformly stirring, sequentially adding the swelled methylcellulose, glycerol and sodium benzoate while stirring, stirring and mixing, finally adding purified water to a constant volume to prepare a liquid medicine, and performing all operations at room temperature; stirring the prepared liquid medicine and homogenizing;
and 5, canning, sealing and sterilizing to prepare the slow-release enrofloxacin suspension.
3. The method for preparing the slow-release enrofloxacin suspension according to the claim 2, characterized in that the glassware used in the method needs to be treated as follows before use: the glass metering instrument should be drained naturally and not baked in an oven; pushing the rest glass instruments into an upper plate of a washing machine, starting the washing machine, placing the glass instruments into an oven for drying after ultrasonic cleaning and purified water washing, and sterilizing according to a specified sterilization program; the pressure of the purified water for washing is more than or equal to 0.2 Mpa; the speed of the motor of the washing machine does not exceed 50 Hz; the temperature in the sterilization stage was 180 ℃ and the sterilization time was 1.5 hours.
4. The preparation method of the slow-release enrofloxacin suspension according to claim 2, wherein the swelling treatment of the methylcellulose in the step 2 is specifically carried out according to the following steps: putting the weighed methylcellulose into a beaker, adding purified water accounting for 30 percent of the total volume of the slow-release enrofloxacin suspension, stirring for 3-4h on a magnetic stirrer, and swelling for later use.
5. The preparation method of the slow-release enrofloxacin suspension according to claim 2, wherein the dispersion treatment of enrofloxacin in the step 3 is specifically: grinding the weighed enrofloxacin for 10-20min, grinding, and adding purified water for dispersion.
6. The preparation method of the slow-release enrofloxacin suspension according to claim 2, wherein the concentration of the sodium hydroxide solution in the step 4 is 2 mol/L.
7. The preparation method of the slow-release enrofloxacin suspension according to the claim 2, wherein the stirring and mixing time in the step 4 is 25-35 min.
8. The preparation method of the slow-release enrofloxacin suspension according to claim 2, wherein the homogenizing the prepared liquid medicine in the step 4 while stirring is specifically as follows: homogenizing at 300-500 bar for 2 times, and regulating pressure to 1600bar for 8 times.
9. The preparation method of the slow-release enrofloxacin suspension according to the claim 2, wherein the sterilization pressure in the step 5 is 0.3-0.6Mpa, the sterilization temperature is 115 ℃, and the time duration is 30 min.
CN202210147063.4A 2022-02-17 2022-02-17 Slow-release enrofloxacin suspension and preparation method thereof Pending CN114557961A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202210147063.4A CN114557961A (en) 2022-02-17 2022-02-17 Slow-release enrofloxacin suspension and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210147063.4A CN114557961A (en) 2022-02-17 2022-02-17 Slow-release enrofloxacin suspension and preparation method thereof

Publications (1)

Publication Number Publication Date
CN114557961A true CN114557961A (en) 2022-05-31

Family

ID=81714273

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210147063.4A Pending CN114557961A (en) 2022-02-17 2022-02-17 Slow-release enrofloxacin suspension and preparation method thereof

Country Status (1)

Country Link
CN (1) CN114557961A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117771175A (en) * 2024-02-23 2024-03-29 中国农业科学院农业环境与可持续发展研究所 Enrofloxacin nano suspension and preparation method and application thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1907261A (en) * 2006-05-22 2007-02-07 青岛康地恩实业有限公司 Long-acting carbostyril family antibacterial drugs suspension injection
CN104721197A (en) * 2013-12-20 2015-06-24 青岛康地恩动物药业有限公司 Enrofloxacin and sulfadiazine silver suspending agent and preparation method thereof
CN107349182A (en) * 2017-05-31 2017-11-17 合肥中龙神力动物药业有限公司 Animal enrofloxacin suspension and preparation method thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1907261A (en) * 2006-05-22 2007-02-07 青岛康地恩实业有限公司 Long-acting carbostyril family antibacterial drugs suspension injection
CN104721197A (en) * 2013-12-20 2015-06-24 青岛康地恩动物药业有限公司 Enrofloxacin and sulfadiazine silver suspending agent and preparation method thereof
CN107349182A (en) * 2017-05-31 2017-11-17 合肥中龙神力动物药业有限公司 Animal enrofloxacin suspension and preparation method thereof

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
刘小艳等: ""恩诺沙星口服混悬液的研制及其对仔猪黄白痢疗的效观察"", 《动物医学进展》 *
吴海坤等: ""恩诺沙星混悬液的研制及其在鸡组织中的残留研究"", 《动物医学进展》 *
王世宇主编: "《药用辅料学 十三五规划》", 30 April 2019, 中国中医药出版社 *
符华林等: ""正交设计优选复方恩诺沙星混悬型注射剂处方的研究"", 《中国畜牧兽医学会动物药品学分会2006学术会议论文集》 *
赵成等: ""恩诺沙星注射混悬剂的研制及药物含量测定研究"", 《中国卫生产业》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117771175A (en) * 2024-02-23 2024-03-29 中国农业科学院农业环境与可持续发展研究所 Enrofloxacin nano suspension and preparation method and application thereof
CN117771175B (en) * 2024-02-23 2024-06-07 中国农业科学院农业环境与可持续发展研究所 Enrofloxacin nano suspension and preparation method and application thereof

Similar Documents

Publication Publication Date Title
CN102772360B (en) Doxycycline hydrochloride injection for animals and preparation method for doxycycline hydrochloride injection
CN114557961A (en) Slow-release enrofloxacin suspension and preparation method thereof
CN109453390B (en) Enrofloxacin hydroxypropyl cyclodextrin inclusion compound and preparation method and application thereof
CN103989630A (en) Moxifloxacin hydrochloride sodium chloride injection and preparation method thereof
CN103816166B (en) Compound doxycycline hydrochloride injection for animals, and its preparation method
CN117379378A (en) Compound amoxicillin soluble powder for livestock and preparation process thereof
CN113197850A (en) Oral suspension of iron glucoheptonate and ponazuril and preparation method thereof
CN103126982A (en) Novel veterinary medicament meglumine enrofloxacin injection and preparation method thereof
CN104721154B (en) Injection norfloxacin glutamate freeze-drying powder-injection pharmaceutical composition
CN109745301A (en) A kind of carbocisteine Neulized inhalation pharmaceutical solutions and preparation method thereof
CN109620804B (en) Ceftriaxone sodium powder injection preparation for injection and preparation method thereof
CN103497225A (en) Tartaric acid mikamycin for injection and preparations and preparation method thereof
CN107789320A (en) A kind of fulvestrant sustained-release parenteral solution and its preparation technology
CN107157926B (en) Preparation method of docetaxel injection
CN113209014A (en) Long-acting cefquinome sulfate suspension injection and preparation process thereof
CN112089696A (en) Marbofloxacin flavor tablet and preparation method thereof
CN106420599B (en) Preparation method of citric acid caffeine injection
CN110742868A (en) Mirogabalin Besilate orally disintegrating tablet
CN105012249A (en) Injection rifampicin and preparing method thereof
CN110898042B (en) Salbutamol sulfate solution for inhalation and preparation method thereof
CN115518035B (en) Ketorolac liquid composition, preparation method and application thereof
CN107823130A (en) A kind of preparation method of tetrandrine injection agent medicine composition
CN106727662B (en) A kind of carboxyl maltose iron Pharmaceutical composition and preparation method thereof
CN110151707B (en) Ropivacaine mesylate pharmaceutical composition and preparation method thereof
CN114767627B (en) Preparation method of ciprofloxacin lactate sodium chloride injection

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
RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20220531