CN105853351B - Linezolid oral administration mixed suspension and preparation method thereof - Google Patents
Linezolid oral administration mixed suspension and preparation method thereof Download PDFInfo
- Publication number
- CN105853351B CN105853351B CN201610202729.6A CN201610202729A CN105853351B CN 105853351 B CN105853351 B CN 105853351B CN 201610202729 A CN201610202729 A CN 201610202729A CN 105853351 B CN105853351 B CN 105853351B
- Authority
- CN
- China
- Prior art keywords
- linezolid
- solution
- suspension
- preparation
- oral administration
- 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.)
- Active
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
- A61K9/10—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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nutrition Science (AREA)
- Dispersion Chemistry (AREA)
- Physiology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to field of pharmaceutical preparations, and in particular to a kind of Linezolid oral administration mixed suspension and preparation method thereof.Linezolid oral administration mixed suspension in the present invention, it in parts by weight include following components: 0.5~2.0 part of Linezolid, 0.5~5.0 part of sodium carboxymethylcellulose, 0.05~0.5 part of polyoxyethylene sorbitan monoleate, 0.15~0.20 part of sodium citrate, 0.08~0.10 part of citric acid, 0.22~0.28 part of preservative, 22~28 parts of sweetener, 1.2~1.8 parts of corrigent and aqueous medium.The present invention has filled up in market the blank for only having tablet, injection, provides new dosage form selection；The Linezolid oral administration mixed suspension good quality of product, and accurate divided dose can be carried out according to weight, it is easy to swallow；Preparation method simple process of the invention, it is feasible, and there is reproducibility, it can the uniform Linezolid oral administration mixed suspension for producing satisfactory quality.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, and in particular to a kind of Linezolid oral administration mixed suspension and preparation method thereof.
Background technique
Linezolid is the antibiotic of the brand new class of first acquisition listing license in Oxazolidinone derivative, by
Upjohn company develops, and 2000, FDA ratified its list marketing, for treating Grain-positive (G+) coccigenic infection, wraps
Include it is doubtful as caused by MRSA or make a definite diagnosis nosocomial pneumonia (HAP), community acquired pneumonia (CAP), complexity skin or
Skin soft-tissue infection (SSTI) and vancomycin-resistant enterococcus (VRE) infection etc..
Linezolid is bacterio protein synthetic inhibitor, acts on bacterium 50S ribosomal subunit, and closest work
Use position.Different from other medicines, Linezolid does not influence peptidyl transferase activity, only acts on the starting rank of translation system
Section inhibits mRNA to connect with ribosomes, the formation of 70S initiation complex is prevented, to inhibit the synthesis of bacterio protein.
Between the Pharmacological Mechanism of Linezolid, in clinical application, patient can be made to obtain biggish interests:
1) be not susceptible to crossing drug resistant: the site of action and mode of Linezolid are unique, therefore with essential or obtain
In the positive bacteria for obtaining property drug-resistance characteristics, all it is not easy and crossing drug resistants occurs for other antimicrobials for inhibiting albumen to synthesize.
2) bioavilability is high: Linezolid is that unique oral administration biaavailability is almost identical with intravenous administration novel
Antibiotic absorbs rapid.Its oral administration biaavailability nearly reaches 100%, when clinic is changed to oral administration from intravenously administrable, nothing
It must carry out dosage adjustment.
3) wide application of the crowd: newborn to gerontal patient can be used.Gerontal patient, different degrees of potential renal insufficiency patient
Dosage adjustment need not be carried out with dyshepatia patient mild to moderate.
4) has a broad antifungal spectrum: there is antibacterial activity to most of bacterial strains, cause a disease including aerobic and facultative Gram-positive
Bacterium, enterococcus faecium (bacterial strain for only referring to drug resistance of vancomycin), staphylococcus aureus (bacterial strain including methicillin resistance), nothing
Streptococcus lactis, streptococcus pneumonia (including the bacterial strain [MDRSP] to multidrug resistance), micrococcus scarlatinae.
5) curative for effect: clinical efficacy is superior to or is equal to conventional antimicrobial drug.And only to specified microorganisms sensitive strain
Caused infection is effective, can prevent the abuse of antibiotic, is that human body is resistance to the generation of the Conventional antibiotics such as vancomycin, methicillin
Ideal chose after pharmacological property is the first choice of nosocomial pneumonia.
The preparation of Linezolid market sale both at home and abroad at present, i.e., clinically drug-delivery preparation be the solid tablet taken orally and quiet
Arteries and veins two kinds of dosage forms of big infusion.Both dosage forms have disadvantage, such as oral solid tablet, although carrying, clinical application, patient's medication
The larger infusion of compliance is convenient, but due to the larger 0.6g of oral tablet specification, in addition auxiliary material, piece is close to 0.9g or so, piece
Excessive, for the patient of children, old man or other dysphagias, medication is difficult；Separately the newborn to 7 days or more or its
For the children of his age bracket, clinical application must by 10mg/kg for every eight hours or 12 hours dosage be administered Linezolid, therefore,
The newborn or children of different weight are according to weight, and the dosage for taking Linezolid is different, but oral tablet is excessive, and
Harder, divided dose is more difficult, and inaccuracy.In addition, the big infusion of vein is for general patient, it is more inconvenient to take medicine, and need to go
Hospital or clinic carry out intravenous drip, and another safety risks are compared with oral preparation height.One is provided in patent of invention CN102973500
Kind of Linezolid liquid preparation and preparation method thereof, group be divided into Linezolid, citric acid, citric acid receive, sodium chloride, injection
Water, said preparation are injection, know that it does not have oral liquid often to use auxiliary material, such as corrigent, sweetener etc. from prescription, complete
It is all injection and often uses auxiliary material；Its method is also the preparation process of injection, non-oral liquid preparation and preparation method thereof.
A kind of preparation method of high stable Linezolid Injection, group are provided in patent of invention CN201310607446.6
It is divided into Linezolid, glucose, sodium dihydrogen phosphate or phosphoric acid, water for injection, said preparation is injection, and method is also injection
Preparation process, non-oral liquid preparation and preparation method thereof.
Patent of invention CN201210525618.0, CN201410401123.6, CN201510567368.0,
A kind of Linezolid oral tablet and preparation method thereof is each provided in CN201210581947.7, CN201110207573.8,
Contained material is tablet routine material, such as mannitol, lactose, microcrystalline cellulose, crospovidone, polyethylene glycol, Bo Luosha
Nurse etc., preparation method are also to be prepared using the common process of tablet.Such oral solid formulation, which still has, to be difficult to point
Dosage inaccuracy, piece cuckoo lattice are difficult to greatly the shortcomings that swallowing after dosage, divided dose.
The freeze-drying buccal tablet and preparation method thereof of children a kind of is provided in patent of invention CN201210732013.3, it should
The materials such as patent prescription receives containing Linezolid, mannitol, gelatin, citric acid, Sucralose, sodium bicarbonate, this patented composition
There is some superiority, without using water, without chewing, 4s clock energy fater disintegration.But still there are children to give Li Nai according to weight
The problem of azoles amine is difficult to divided dose；Even if another oral disnitegration tablet of the present invention is fast again, the redisperse after solid state is disintegrated also is needed
Process and play drug effect, compared with liquid preparation, it is still relatively slow that disintegration plays curative effect.In addition, the present invention uses freeze-drying mode
Tablet is prepared, needs special freeze drying equipment, process cycle long and complicated, manufacturing cost height, Linezolid main ingredient specification itself
It is larger, for example listing oral tablet main ingredient specification is 0.6g, cost of material is high, along with the manufacturing cost of great number, necessarily to trouble
Person increases financial burden.
It is carried between high-capacity injection, clinical application inconvenience, patient's poor compliance, oral solid formulation is difficult to a point agent
The feature of amount or divided dose inaccuracy, therefore, it is necessary to develop, a kind of medication is convenient, be easy to divided dose and dosage is accurate at present
Preparation.Linezolid suspension oral solution of the invention can fill up this blank, be Grain-positive (G+) coccigenic infected patient
There is provided that a kind of carrying convenience, medication is convenient, is easy to the oral liquid of divided dose.
Summary of the invention
In view of this, the purpose of the present invention is to provide benefit made from a kind of Linezolid composition and preparation method how azoles
Amine oral administration mixed suspension has been filled up in market and has only had the blank of tablet, injection, provided new dosage form selection；The Linezolid
Oral administration mixed suspension good quality of product；And accurate divided dose can be carried out according to weight, be easy to swallow, for children, old man and other
Dysphagia patients are provided convenience；Preparation method of the invention shows the simple process through pilot scale and trial production amplification, can
Row, and there is reproducibility, it can the uniform Linezolid oral administration mixed suspension for producing satisfactory quality.
To achieve the above object, the technical solution of the present invention is as follows:
A kind of Linezolid oral administration mixed suspension includes following components in parts by weight: 0.5~2.0 part of Linezolid, carboxylic
0.5~5.0 part of sodium carboxymethylcellulose pyce, pH combines 0.23~0.30 part of regulator and aqueous medium.
As a preference, the Linezolid is Linezolid micro mist.
Suspension oral solution is to determine that Linezolid is polymorph medicine according to the dissolution characteristics of main ingredient in water, is used at present
It is usually that II type crystalline substance familial combined hyperlipidemia is brilliant, wherein II type crystalline substance is the most stable, IV type crystalline substance is easily converted into II type in damp and hot situation in preparation
It is brilliant.The dissolubility of two kinds of crystal forms is essentially identical, is slightly soluble drug, and solubility is smaller in water, (is shown in Table for 3.0mg/ml or so
1, table 2), therefore, the Linezolid of 0.6g main ingredient specification is prepared into solution-type injection or oral solution, 200ml water is at least needed,
Easy crystallization is placed for 2~8 DEG C under this concentration conditions, and the concentration of dissolution is bigger, is more saturated, and crystallization is more serious (being shown in Table 3).In order to protect
Main ingredient not crystallization body after card dissolution, at least wants 300ml or more, and the Linezolid Injection listed such as import is 300ml:0.6g
Main ingredient or 150ml:0.3g main ingredient.As it can be seen that this is for suffering from if being made into solution-type oral solution at least needs 300ml or 150ml water
Person is difficult to receive, especially children, and liquor capacity is too big, poor compliance.Therefore, it in order to improve patient's compliance, is prepared into often
The oral solution for advising small size specification (such as 5ml, 10ml), in combination with Linezolid solubility, this product is only suitable for preparation and is suspended
Type oral solution, rather than solution-type oral solution.
The apparent solubility of table 1 crystal form II and crystal form IV
| Solvent | II solubility of crystal form (mg/ml) | IV solubility of crystal form (mg/ml) | Dissolubility |
| Water | 2.8 | 3.0 | Slightly soluble |
2 bulk pharmaceutical chemicals of table dissolve situation in different pH value aqueous solutions
| Medium | Water | pH1.1 | pH4.0 | pH5.0 |
| Solubility | 1mg/100ml | 0.1mg/100ml | 0.1mg/100ml | 0.2mg/100ml |
Dissolubility under 3 distinct temperature of table investigates result
Note: "-" expression has no that crystal is precipitated, and "+" indicates that slightly having crystal is precipitated, and multiple "+" indicate that serious journey is precipitated in crystal
Degree.
Linezolid particle is in normal distribution in the Linezolid oral administration mixed suspension.
Sodium carboxymethylcellulose is suspending agent in the Linezolid oral administration mixed suspension, and suspending agent is more crucial, effect
Predominantly suspending is slowly settled after shaking particulate matter, is suspended in solution, is avoided settling too fastly between particle, is sunken to bottom
Tessellation occurs for portion, sized particles, and long-term place occurs particle caking phenomenon, influence drug quality.Common suspending agent has
Gelatin, Arabic gum, xanthan gum, polyvinylpyrrolidone, sodium carboxymethylcellulose, hypromellose etc..Variety classes
Suspending agent there is different physicochemical properties, such as viscosity, surface charge, and active constituent compatibility.The preferred carboxylic first of the present invention
Base sodium cellulosate, after dissolving clarification in water because of sodium carboxymethylcellulose, negative electrical charge on solution band, when particulate matter main ingredient adds
After solution, negative electrical charge uniform on microparticle surfaces band can be made, this is conducive to the physical stability of particle, arranges each other between particle
Reprimand avoids particle agglomeration, is conducive to product and stablizes.
Sodium carboxymethylcellulose is as suspending agent, and the concentration of suspending agent also influences the suspending effect of particle, and concentration is bigger, helps
The viscosity of suspension is stronger, and suspending effect is better, but concentration is excessive, and viscosity is too strong, will cause filtration difficulty, glues chamber wall, residual
Measure excessive problem；Suspending agent concentration is too low, viscosity it is too small, and will cause suspended particles sedimentation resistance it is small, settle it is too fast, it is unfavorable
It is administered when clinical application complete.In addition, particle self property and size, suspending agent type and dosage can be to productions as previously described
The suspension flocculating effect of product has an impact, and the two has certain relativity, if particle is big, weight, and inevitable requirement suspending agent concentration
Relatively a little bigger, viscosity enough in this way could prevent the rapid subsidence of particle, anyway, particle is small, gently, it is only necessary to be suitable for smaller concentration
Suspending agent can reach effective flocculation and suspending effect.The selection of particle size of the present invention and suspending agent, from the prior art
It is difficult to be prompted and implied well, it is necessary to by obtained by a large amount of experiment sieving.It is big in phase Linezolid particle of the present invention
In small and sodium carboxymethylcellulose concentration range, product suspension solution sedimentation volume ratio is made and is all larger than 0.95 (2015 editions pharmacopeia
It is required that being 0.9~1.0), sedimentation volume ratio is bigger, shows that flocculating effect is better, and it is more loose between particle, it is cotton-shaped in cotton, have
It conducive to the stabilization of particle, does not agglomerate, also without caking phenomenon after long-term 40 DEG C of placements June.And comparative example 1, comparative example 2
Middle product flocculating effect is poor, and sedimentation volume ratio only has 0.83,0.75, has caking phenomenon after long-term 40 DEG C of placements June.
Further, Linezolid particle size D90 is 10~150 μm in the Linezolid oral administration mixed suspension.
As previously mentioned, solubility is smaller in water for Linezolid, it is suitable for preparing suspension oral solution, therefore Linezolid is in mouth
It takes in liquid with the presence of particle hybrid state.Particle size and uniformity will affect the physically stable of mixed suspension preparation in mixed suspension preparation
Property, such as agglomeration problems in storage process.Particle is excessive, overweight, and sinking speed is too fast, and product is placed for a long time is easy agglomeration；In addition
If drug microparticles are quickly sunken to bottom, it is complete that when clinical application, is not easy to medication.Particle is too small, though it is conducive to suspend in the solution,
But it is too small to accelerate its dissolution, recrystallization is easily caused after dissolution, crystal is grown up, to influence product quality；Another particle is meticulous, than
Surface area increases, and surface free energy increases, and particle gathers unstability with stronger, is easier to again agglomerated together tie
Block phenomenon.The control of Linezolid diameter of particle is 10~150 μm in D90 in the present invention, and particle is in normal distribution, can effectively be avoided
Particle it is excessive it is too small caused by agglomeration problems.
As a preference, Linezolid particle size D90 is 50~100 μm in the Linezolid oral administration mixed suspension.
Further, the pH value of the Linezolid oral administration mixed suspension is 4.2~5.2.
As a preference, the pH value of the Linezolid oral administration mixed suspension is 4.9.
The stability of Linezolid in water, has with pH compared with Important Relations, research shows that Linezolid is within the scope of 4.2-5.2
Stability is relatively preferably (being shown in Table 4).PH adjusting agent of the present invention is selected as sodium citrate and citric acid, and sodium citrate and the Chinese holly
The weight part ratio of rafter acid are as follows: 0.15~0.20:0.08~0.10, and the oral solution pH value obtained is comparatively fixed, pH value exists
4.9 or so, it is the optimal pH of Linezolid stability.
Steadiness of 4 Linezolid of table in different pH value
Further, the pH combination specific ingredient of regulator is sodium citrate and citric acid, the sodium citrate with it is described
The weight part ratio of citric acid are as follows: 0.15~0.20:0.08~0.10.
Technique is adjusted according to Linezolid chemical stabilization implementations, while in order to simplify pH, the present invention combines regulator and is
Sodium citrate and citric acid, there are also another key factor, pH value combination is adjusted for the selection of sodium citrate and citric acid of the present invention
Opalescence phenomenon will not be generated to this product suspension oral solution by saving agent, and oral administration solution can cream when selecting phosphoric acid salt pH adjusting agent
Optical phenomenon influences product quality.In addition, oral solution of the present invention is suitable for children, therefore, from the aspect of mouthfeel, citron is selected
Sour sodium and citric acid, opposite mouthfeel are easier to receive.
Further, the Linezolid oral administration mixed suspension further includes wetting agent, preservative, sweetener and corrigent；It is described
Wetting agent is polysorbate, and the preservative is sodium benzoate, and the sweetener is sorbierite, and the corrigent is that cherry powder is fragrant
Essence.
Wetting agent in the present invention selects polyoxyethylene sorbitan monoleate, and polyoxyethylene sorbitan monoleate is nonionic surface active agent, Ke Yigai
The wetability of kind surface of drug particles, and the change of high concentration electrolyte and pH value is to influence very little.Linezolid microparticle surfaces
With hydrophobicity, after being added in water, it is suspended in water surface, it is difficult to be spontaneously wet out by water dispersion, therefore select polyoxyethylene sorbitan monoleate conduct
Wetting agent can reduce the interfacial tension of particle and water very well, and Linezolid particle is made to achieve the purpose that effective wetting, with benefit how
Azoles amine has good chemical compatibility, does not chemically react with Linezolid.
Particulate chemistry stability is different, and the hydrophobic ability of microparticle surfaces is different, and particle size is different, inevitable Surfactant
Type selection it is different with dosage.If kinds of surfactants of the present invention selects polyoxyethylene sorbitan monoleate, have with Linezolid good
Good chemical compatibility, does not chemically react with Linezolid；Hydrophobic performance and present invention benefit according further to Linezolid
How the particle size range of azoles amine particle, select the dosage of polyoxyethylene sorbitan monoleate, hydrophobicity needs more by force polyoxyethylene sorbitan monoleate dosage bigger, particle
Smaller, surface area is bigger, and required polyoxyethylene sorbitan monoleate dosage is bigger, and the present invention has finally determined the use of polyoxyethylene sorbitan monoleate by screening
Amount.
The present invention is according to the bacteriostasis of Linezolid itself and the bacteriostatic test of product oral liquid, preservative final choice
Sodium benzoate and its dosage can reach effective anti-corrosion effect, and have good physical chemistry compatibility with Linezolid, no
Adverse effect can be generated to product suspension effect and content, related substance.
The range of choice of oral solution sweetener and corrigent is wider, for example common Aspartame of sweetener, saccharin sodium, trichlorine
Sucrose, honey element, Stevioside, essence etc..The present invention selects sorbierite that can effectively improve the mouthfeel of oral solution, has refrigerant sense,
It is particularly suitable for old man and children, compliance is preferable, and good with Linezolid chemical compatibility, the dosage of the sorbierite of selection
Optimal mouthfeel effect can be reached.The corrigent present invention selects U.S. kerry cherry powder essence, and mouthfeel is cherry-flavored, is particularly suited for
The mouthfeel of children shows that the cherry powder essence and its dosage do not interfere the oral liquid hold-up of the present invention and related by compatibility test
The measurement of substance, it is good with Linezolid compatibility, its chemical stability is not influenced.
Other more sweeteners or corrigent in addition to sorbierite of the present invention, cherry powder, such as saccharin sodium, Aspartame, sweet tea
Sweet element etc. is unfavorable for the stability of Linezolid in oral solution or can interfere quality determining method content or the measurement in relation to substance,
Therefore final choice sorbierite of the present invention and cherry powder essence are the best sweetener and corrigent of Linezolid oral solution.
Further, the Linezolid oral administration mixed suspension is composed of the following components in parts by weight: Linezolid 0.5~
2.0 parts, 0.5~5.0 part of sodium carboxymethylcellulose, 0.05~0.5 part of polyoxyethylene sorbitan monoleate, 0.15~0.20 part of sodium citrate, Chinese holly
0.08~0.10 part of rafter acid, 0.22~0.28 part of sodium benzoate, 22~28 parts of sorbierite, 1.2~1.8 parts of cherry powder essence and water
Medium.
As a preference, the Linezolid oral administration mixed suspension is composed of the following components in parts by weight: benefit how azoles
0.5~2.0 part of amine, 2.0~5.0 parts of sodium carboxymethylcellulose, 0.2~0.4g parts of polyoxyethylene sorbitan monoleate, 0.18 part of sodium citrate,
0.09 part of citric acid, 0.25 part of preservative, 25 parts of sweetener, 1.5 parts of corrigent and aqueous medium.
The second object of the present invention is to provide a kind of preparation method of Linezolid oral administration mixed suspension, including following step
It is rapid:
1) it takes the sodium carboxymethylcellulose of above-mentioned parts by weight to be dissolved in aqueous medium, obtains solution I after completely dissolution；
2) polyoxyethylene sorbitan monoleate of above-mentioned parts by weight is added into solution I described in step 1), stirs dissolved clarification, obtains solution II；
3) Linezolid of above-mentioned parts by weight is added into solution II described in step 2), mixes well, flocculates, obtains suspension
Ⅲ；
4) sodium citrate and citric acid of above-mentioned parts by weight are added into suspension III described in step 3), adjusts pH value, obtains
Suspension IV；
5) preservative of above-mentioned parts by weight, sweetener and corrigent are added into suspension IV described in step 4), after dissolved clarification
Up to suspension oral solution finished product.
Further, the step 1) sodium carboxymethylcellulose first disperses in room temperature purified water, is heated under stirring condition
80-100 DEG C of swelling clarification, is cooled to room temperature, obtains solution I.
Sodium carboxymethylcellulose is high-molecular compound, is swollen in cold water relatively slow, and 80 DEG C or more can comparatively fast be swollen and be
Macromolecule glue liquid solution, and the Polymer Solution is more stable in 100 DEG C, and auxiliary material degradation impurity peak will not occur.It is cooled to room
The purpose of temperature is conducive to the physical and chemical stability of subsequent addition polyoxyethylene sorbitan monoleate and Linezolid, disperses particle preferably
Flocculation, reaches optimal volume settling ratio.
Further, the weight part ratio of the step 1) sodium carboxymethylcellulose and aqueous medium are as follows: 0.5~5.0:65~75.
Further, Linezolid is Linezolid micro mist in step 3), and Linezolid micro mist, homogeneous are added into solution II
5000~8000rpm of speed disperses 5~10min, mixes, and flocculation obtains suspension III.
The homogeneous speed is key process parameter, it is necessary to have enough intensity to make Linezolid micro mist and polyoxyethylene sorbitan monoleate
It comes into full contact with, reduces its microparticle surfaces tension, achieve the purpose that full and uniform dispersion, wetting.This processing step need to be with equal
It is carried out in the jar of matter equipment, and homogeneous speed need to control within the scope of the invention, revolving speed is too low, and homogenizing time is too short, micro-
Dispersion moistening effect is not achieved in grain；Revolving speed is excessive or homogenizing time is too long, because containing polyoxyethylene sorbitan monoleate surface-active containing suspension
Agent, is also easy to produce a large amount of foams, is also unfavorable for the dispersion, wetting, flocculation of particle.Though that the present invention is homogenizer, this behaviour
It is not limited to homogenizer, all dispersion, wettings, wadding that can generate the achievable particle of the present invention of the equipment acutely vibrated
It is solidifying, such as using ultrasonic equipment, mixing plant, the magnetic stirring apparatus of larger revolving speed power.Different pharmaceutical particle, superficiality
Matter is different (such as hydrophobicity is different), the different (types of such as wetting agent and suspending agent and dense of the required supplementary product kind for preparing suspension
Degree is different), suspension matrix is variant, and corresponding homogeneous strength demand is necessarily caused to change.As 5000 in the present invention~
Need homogeneous 5 minutes or more, preferably 5~10 minutes under 8000rpm homogeneous speed, under this intensity and time conditions, Linezolid is micro-
Grain could fully dispersed, wetting, flocculation, it is best to obtain product flocculating effect, stable product quality, and long-term place will not occur
Caking phenomenon.
Further, step 4) the adjusting pH value is 4.2~5.2.
In the preparation method, after flocculation is added in Linezolid particle, pH adjusting agent sodium citrate and citron is just added
Acid is to adjust pH value to 4.2~5.2, it is therefore intended that makes negative electrical charge uniform on Linezolid particle band.Because of Linezolid particle
It, can only be with single charge after particle feeds intake only containing a kind of electrically charged material of sodium carboxymethylcellulose in solution before feeding intake
Contact, so that microparticle surfaces be made all to take uniform charge.If pH adjusting agent sodium citrate is incorporated in advance with citric acid
Linezolid particle is added in carboxymethylcellulose sodium solution, after dissolution；This technique, because sodium citrate is inorganic with citric acid
Salt can will be completely dissociated in the solution as positive and negative charge, put into drug microparticles at this time, some particles can be positively charged than so, part
It is negatively charged, it is easy to happen attracting between the particle of this belt transect positive and negative charge, to influence product quality, long-term particle of placing is easy
Agglomeration problems are generated, if product flocculating effect is poor in comparative example 3, sedimentation volume ratio only has 0.90, and long-term 40 DEG C of product put
It agglomerates after setting June.It therefore is first to throw Linezolid in the carboxymethylcellulose sodium solution of single charge in preparation method of the present invention
In, make its dispersion, take uniform negative electrical charge, after flocculating completely, adds pH adjusting agent sodium citrate and citric acid, be conducive to
Product flocculation is stablized, and is not agglomerated.
It is fragrant that preservative sodium benzoate, sweetener sorbierite and corrigent cherry powder is finally added in the present invention into suspension
Essence, purpose is as previously mentioned, also for positive and negative charge inhomogenous on Linezolid band is avoided, and there is a natural attraction between the sexes for generation, and agglomeration is existing
As influencing product quality.
The beneficial effects of the present invention are: Linezolid oral administration mixed suspension of the invention is stablized with good physical chemistry
Property, sedimentation volume ratio height, good fluidity, no caking phenomenon and other quality index are good, show good quality of product；This hair
Bright preparation method shows the simple process through pilot scale and trial production amplification, feasible, and has reproducibility, can be uniform
Produce the Linezolid oral administration mixed suspension of satisfactory quality.
1. the present invention provides a kind of Linezolid new oral formulation, i.e. Linezolid oral administration mixed suspension has filled up city
Field blank (market only has tablet, injection) provides new dosage form choosing for Grain-positive (G+) coccigenic infected patient
It selects；The country has been carried out industrialization, and price is relatively cheap, is truly realized super quality and competitive price, for such patient significantly reduce through
Ji burden.
2. suspension oral solution provided by the invention is that one kind is rapid-action, quality stability is good, and no opalescence does not agglomerate, produces
Product content, related substance are stablized, clinical safety and the good oral administration mixed suspension of curative effect.
3. suspension oral solution provided by the invention can provide the compliance of dysphagia patients significantly, convenient for swallowing medication,
Divided dose and correct dose administration, are particularly suitable for children and gerontal patient.
4. suspension oral solution carrying convenience of the invention, be conducive to accurate divided dose, be particularly suitable for children according to weight into
The administration metering of row Linezolid.
Specific embodiment
It detailed description of a preferred embodiment of the present invention will be given below.The reality of actual conditions is not specified in preferred embodiment
Proved recipe method, usually according to normal condition, illustrated embodiment are but not to be to preferably be illustrated to the contents of the present invention
The contents of the present invention are only limitted to illustrated embodiment.So those skilled in the art are according to foregoing invention content to embodiment party
Case carries out nonessential modifications and adaptations, still falls within protection scope of the present invention.
1 Linezolid oral mixed suspension formula of liquid 1 of embodiment and preparation method
(1) preparation prescription: (1000ml is made altogether)
(2) preparation method:
1) 4/5 recipe quantity purified water is weighed, recipe quantity suspending agent sodium carboxymethylcellulose is added on wherein, 80- is heated to
100 DEG C, stirring swelling clarification is cooled to room temperature, obtains solution I；
2) wetting agent polyoxyethylene sorbitan monoleate is added into solution I, stirs dissolved clarification, obtains solution II；
3) Linezolid micro mist is added into solution II again, homogeneous 5000rpm disperses 5min, mixes, and flocculation obtains suspension
Ⅲ；
4) pH adjusting agent sodium citrate and citric acid are added into suspension III, obtains suspension IV；
5) preservative sodium benzoate, sweetener sorbierite and the corrigent cherry of recipe quantity are finally added into suspension IV
Powder essence, 30Hz stirs 10min, and after dissolved clarification, water supplement to 1000ml is to get suspension oral solution finished product.
2 Linezolid oral mixed suspension formula of liquid 2 of embodiment and preparation method
(1) preparation prescription: (1000ml is made altogether)
(2) preparation method:
1) 4/5 recipe quantity purified water is weighed, recipe quantity suspending agent sodium carboxymethylcellulose is added on wherein, 80- is heated to
100 DEG C, stirring swelling clarification is cooled to room temperature, obtains solution I；
2) wetting agent polyoxyethylene sorbitan monoleate is added into solution I, stirs dissolved clarification, obtains solution II；
3) Linezolid micro mist is added into solution II again, homogeneous 5000rpm disperses 8min, mixes, and flocculation obtains suspension
Ⅲ；
4) pH adjusting agent sodium citrate and citric acid are added into suspension III, obtains suspension IV；
5) preservative sodium benzoate, sweetener sorbierite and the corrigent cherry of recipe quantity are finally added into suspension IV
Powder essence, 30Hz stirs 10min, and after dissolved clarification, water supplement to 1000ml is to get suspension oral solution finished product.
3 Linezolid oral mixed suspension formula of liquid 3 of embodiment and preparation method
(1) preparation prescription: (1000ml is made altogether)
(2) preparation method:
1) 4/5 recipe quantity purified water is weighed, recipe quantity suspending agent sodium carboxymethylcellulose is added on wherein, 80- is heated to
100 DEG C, stirring swelling clarification is cooled to room temperature, obtains solution I；
2) wetting agent polyoxyethylene sorbitan monoleate is added into solution I, stirs dissolved clarification, obtains solution II；
3) Linezolid micro mist is added into solution II again, homogeneous 5000rpm disperses 8min, mixes, and flocculation obtains suspension
Ⅲ；
4) pH adjusting agent sodium citrate and citric acid are added into suspension III, obtains suspension IV；
5) preservative sodium benzoate, sweetener sorbierite and the corrigent cherry of recipe quantity are finally added into suspension IV
Powder essence, 30Hz stirs 10min, and after dissolved clarification, water supplement to 1000ml is to get suspension oral solution finished product.
4 Linezolid oral mixed suspension formula of liquid 4 of embodiment and preparation method
(1) preparation prescription: (1000ml is made altogether)
(2) preparation method:
1) 4/5 recipe quantity purified water is weighed, recipe quantity suspending agent sodium carboxymethylcellulose is added on wherein, 80- is heated to
100 DEG C, stirring swelling clarification is cooled to room temperature, obtains solution I；
2) wetting agent polyoxyethylene sorbitan monoleate is added into solution I, stirs dissolved clarification, obtains solution II；
3) Linezolid micro mist is added into solution II again, homogeneous 5000rpm disperses 10min, mixes, and flocculation must suspend
Liquid III；
4) pH adjusting agent sodium citrate and citric acid are added into suspension III, obtains suspension IV；
5) preservative sodium benzoate, sweetener sorbierite and the corrigent cherry of recipe quantity are finally added into suspension IV
Powder essence, 30Hz stirs 10min, and after dissolved clarification, water supplement to 1000ml is to get suspension oral solution finished product.
5 Linezolid oral mixed suspension formula of liquid 5 of embodiment and preparation method
(1) preparation prescription: (1000ml is made altogether)
(2) preparation method:
1) 4/5 recipe quantity purified water is weighed, recipe quantity suspending agent sodium carboxymethylcellulose is added on wherein, 80- is heated to
100 DEG C, stirring swelling clarification is cooled to room temperature, obtains solution I；
2) wetting agent polyoxyethylene sorbitan monoleate is added into solution I, stirs dissolved clarification, obtains solution II；
3) Linezolid micro mist is added into solution II again, homogeneous 5000rpm disperses 10min, mixes, and flocculation must suspend
Liquid III；
4) pH adjusting agent sodium citrate and citric acid are added into suspension III, obtains suspension IV；
5) preservative sodium benzoate, sweetener sorbierite and the corrigent cherry of recipe quantity are finally added into suspension IV
Powder essence, 30Hz stirs 10min, and after dissolved clarification, water supplement to 1000ml is to get suspension oral solution finished product.
6 Linezolid oral mixed suspension formula of liquid 6 of embodiment and preparation method
(1) preparation prescription: (1000ml is made altogether)
(2) preparation method:
1) 4/5 recipe quantity purified water is weighed, recipe quantity suspending agent sodium carboxymethylcellulose is added on wherein, 80- is heated to
100 DEG C, stirring swelling clarification is cooled to room temperature, obtains solution I；
2) wetting agent polyoxyethylene sorbitan monoleate is added into solution I, stirs dissolved clarification, obtains solution II；
3) Linezolid micro mist is added into solution II again, homogeneous 5000rpm disperses 10min, mixes, and flocculation must suspend
Liquid III；
4) pH adjusting agent sodium citrate and citric acid are added into suspension III, obtains suspension IV；
5) preservative sodium benzoate, sweetener sorbierite and the corrigent cherry of recipe quantity are finally added into suspension IV
Powder essence, 30Hz stirs 10min, and after dissolved clarification, water supplement to 1000ml is to get suspension oral solution finished product.
7 Linezolid oral mixed suspension formula of liquid 7 of embodiment and preparation method
(1) preparation prescription: (1000ml is made altogether)
(2) preparation method:
1) 4/5 recipe quantity purified water is weighed, recipe quantity suspending agent sodium carboxymethylcellulose is added on wherein, 80- is heated to
100 DEG C, stirring swelling clarification is cooled to room temperature, obtains solution I；
2) wetting agent polyoxyethylene sorbitan monoleate is added into solution I, stirs dissolved clarification, obtains solution II；
3) Linezolid micro mist is added into solution II again, homogeneous 5000rpm disperses 10min, mixes, and flocculation must suspend
Liquid III；
4) pH adjusting agent sodium citrate and citric acid are added into suspension III, obtains suspension IV；
5) preservative sodium benzoate, sweetener sorbierite and the corrigent cherry of recipe quantity are finally added into suspension IV
Powder essence, 30Hz stirs 10min, and after dissolved clarification, water supplement to 1000ml is to get suspension oral solution finished product.
Comparative example 1
(1) preparation prescription: (1000ml is made altogether)
(2) preparation method:
1) 4/5 recipe quantity purified water is weighed, recipe quantity suspending agent gelatin is added on wherein, heating stirring swelling clarification is cold
But to room temperature, solution I is obtained；
2) wetting agent polyoxyethylene sorbitan monoleate is added into solution I, stirs dissolved clarification, obtains solution II；
3) Linezolid micro mist is added into solution II again, homogeneous 4000rpm disperses 4min, mixes, and flocculation obtains suspension
Ⅲ；
4) pH adjusting agent sodium citrate and citric acid are added into suspension III, obtains suspension IV；
5) preservative sodium benzoate, sweetener sorbierite and the corrigent saccharin of recipe quantity are finally added into suspension IV
Sodium, after dissolved clarification, water supplement to 1000ml is to get suspension oral solution finished product.
Comparative example 2
(1) preparation prescription: (1000ml is made altogether)
(2) preparation method:
1) 4/5 recipe quantity purified water is weighed, recipe quantity suspending agent sodium carboxymethylcellulose is added on wherein, 80- is heated to
100 DEG C, stirring swelling clarification is cooled to room temperature, obtains solution I；
2) wetting agent polyoxyethylene sorbitan monoleate is added into solution I, stirs dissolved clarification, obtains solution II；
3) Linezolid micro mist is added into solution II again, homogeneous 9000rpm disperses 11min, mixes, and flocculation must suspend
Liquid III；
4) pH adjusting agent sodium citrate and citric acid are added into suspension III, obtains suspension IV；
5) preservative sodium benzoate, sweetener sorbierite and the corrigent saccharin of recipe quantity are finally added into suspension IV
Sodium, after dissolved clarification, water supplement to 1000ml is to get suspension oral solution finished product.
Comparative example 3
(1) preparation prescription: (1000ml is made altogether)
(2) preparation method:
1) 4/5 recipe quantity purified water is weighed, recipe quantity suspending agent sodium carboxymethylcellulose is heated to 80-100 DEG C, stirring
Swelling clarification, is cooled to room temperature, obtains solution I；
2) the wetting agent polyoxyethylene sorbitan monoleate, pH adjusting agent sodium citrate and citric acid, anti-corrosion of recipe quantity are added into solution I
Agent sodium benzoate, sweetener sorbierite and corrigent cherry powder essence stir dissolved clarification, obtain solution II；
3) Linezolid micro mist is added into solution II again, homogeneous 9000rpm disperses 11min, mixes, flocculation, water supplement
To 1000ml to get suspension oral solution finished product.
The identification of 8 Linezolid oral administration mixed suspension product quality of embodiment
Using Linezolid oral administration mixed suspension made from the present composition and preparation method, there is good physical chemistry
Stability, sedimentation volume ratio height, good fluidity, no caking phenomenon and other quality index are good, show good quality of product；
After 40 DEG C of acceleration June are investigated, product quality, still without significant change, again showed that product of the present invention quality stability compared with 0 day
Well, superior in quality, specific see Table 5 for details, table 6.
50 day quality condition of Linezolid oral administration mixed suspension of the present invention of table
The Linezolid oral administration mixed suspension of the present invention of table 6 accelerates quality condition after 40 DEG C of June
Sedimentation volume ratio measuring method: referring to " Chinese Pharmacopoeia " annex I in 2015, apparatus plug graduated cylinder measured embodiment sample
50ml, close plug firmly shake 1 minute, record the beginning height Ho of suspension, and after standing 3 hours, observation sedimentation face no longer changes
When sediment height H, sedimentation volume ratio F are as follows: F=H/Ho, concrete outcome are shown in Table 4.According to the evaluation mark of oral administration mixed suspension
Standard, sedimentation volume ratio then show that drug microparticles are uniformly dispersed, flocculating effect is good, good quality of product closer to 1.From table 4, table 5
In as can be seen that sedimentation volume ratio of the embodiment of the present invention be all larger than 0.95, meet States Pharmacopoeia specifications be not less than 0.90 requirement, phase
To comparative example sedimentation volume ratio 0.75-0.90, product of the present invention quality is obviously excellent.
Centrifuge-redisperse number: Example sample 25ml has in plug centrifuge tube as 50ml, and 4000 revs/min, centrifugation
After 30min, to take out, then test tube bottom is inverted, then back and forth back and forth, is counted as 1 time along setting again by fixed centrifugation nozzle, until
Micro-filtration cake is completely dispersed flocculation again, records dispersion number used, and the redispersibility of product is evaluated with it.Centrifugal dispersion number
It is fewer, show that product particles flocculate effect is good, it is prevented from caking between particle.From table 4, table 5 as can be seen that the embodiment of the present invention from
Heart dispersion number is respectively less than 15 times, 20-28 number of relative contrast's embodiment Centrifugal dispersion, hence it is evident that number is few.It is another to add by 40 DEG C
Speed test is it is found that without caking phenomenon after 40 DEG C of product of embodiment of the present invention high temperature storage June, and comparative example occurs
Agglomeration, therefore product of the present invention quality is substantially better than comparative example.
Content assaying method: HPLC method, octadecyl silane are filler, 3 μm of YMC ODS-A4.6 × 150mm；
UV detector: 254nm；Column temperature: 25 DEG C；Sampling volume: 10 μ l；Mobile phase A: trifluoroacetic acid aqueous solution (takes 10%
Trifluoroacetic acid solution 9ml is added to 1000ml water)；Mobile phase B: trifluoracetic acid acetonitrile solution (takes 10% trifluoroacetic acid solution 9ml
It is added in 1000ml acetonitrile)；Flow velocity: 1.0ml/min.Precision measures this product 5ml, sets in 100ml measuring bottle, adds 10% acetonitrile molten
Liquid is diluted to scale, shakes up, and precision measures 10 μ l and injects liquid chromatograph, records chromatogram；Another precision weighs Linezolid pair
It according to product 10mg, is placed in 100ml measuring bottle, scale is dissolved and be diluted to 10% acetonitrile solution, is shaken up, as reference substance solution,
It is measured in the same method, the content of Linezolid (C16H20FN3O4) in test sample is calculated by external standard method.Stable content of the embodiment of the present invention
Property it is good, 40 DEG C of acceleration contents in June are with 0 day without significant change, and comparative example 1, content are decreased obviously.
Related substance-measuring method: inspection method HPLC method；Runing time 43min；Chromatographic condition and system suitability are same
Containing under quantifier；Take the test sample stock solution under content determination item as test solution；Precision measures pair under content determination item
It according to product solution 1ml, sets in 100ml measuring bottle, with 10% dilution in acetonitrile to scale, shakes up, as contrast solution.According to content determination item
Under chromatographic condition, take 10 μ l of contrast solution inject liquid chromatograph, adjust detector sensitivity, make the peak height at principal component peak about
It is the 20%~25% of full scale, precision measures test solution and each 10 μ l of contrast solution, it is injected separately into liquid chromatograph,
Record chromatogram.If any impurity peaks in test sample, calculated by the external standard method of the correction up factor, single impurity peak area is not greater than
2 times (0.2%) of contrast solution main peak area, the sum of each impurity peak area are not greater than 5 times of contrast solution main peak area
(0.5%).The related material stability of the embodiment of the present invention is good, and 40 DEG C of acceleration contents in June, without significant change, and were compared with 0 day
Embodiment 1, related substance obviously increase.
Finally, it is stated that the above examples are only used to illustrate the technical scheme of the present invention and are not limiting, although referring to compared with
Good embodiment describes the invention in detail, those skilled in the art should understand that, it can be to skill of the invention
Art scheme is modified or replaced equivalently, and without departing from the objective and range of technical solution of the present invention, should all be covered at this
In the scope of the claims of invention.
Claims (5)
1. Linezolid oral administration mixed suspension, which is characterized in that composed of the following components in parts by weight: Linezolid 0.5~
2.0 parts, 0.5~5.0 part of sodium carboxymethylcellulose, 0.05~0.5 part of polyoxyethylene sorbitan monoleate, 0.15~0.20 part of sodium citrate, Chinese holly
0.08~0.10 part of rafter acid, 0.22~0.28 part of sodium benzoate, 22~28 parts of sorbierite, 1.2~1.8 parts of cherry powder essence and water
Medium；
The pH value of the Linezolid oral administration mixed suspension is 4.2~5.2；
Linezolid particle size D90 is 50~150 μm in the Linezolid oral administration mixed suspension.
2. the preparation method of Linezolid oral administration mixed suspension, which comprises the following steps:
1) it takes the sodium carboxymethylcellulose of above-mentioned parts by weight to be dissolved in aqueous medium, obtains solution I after completely dissolution；
2) polyoxyethylene sorbitan monoleate of above-mentioned parts by weight is added into solution I described in step 1), stirs dissolved clarification, obtains solution II；
3) Linezolid of above-mentioned parts by weight is added into solution II described in step 2), mixes well, flocculates, obtains suspension III；
4) sodium citrate and citric acid of above-mentioned parts by weight are added into suspension III described in step 3), adjusts pH value, must be suspended
Liquid IV；
5) preservative of above-mentioned parts by weight, sweetener and corrigent are added into suspension IV described in step 4), after dissolved clarification to obtain the final product
Suspension oral solution finished product.
3. preparation method according to claim 2, which is characterized in that the step 1) sodium carboxymethylcellulose is first in room temperature
Disperse in purified water, 80-100 DEG C of swelling clarification is heated under stirring condition, is cooled to room temperature, obtains solution I.
4. preparation method according to claim 2, which is characterized in that the step 1) sodium carboxymethylcellulose and aqueous medium
Weight part ratio are as follows: 0.5~5.0:65~75.
5. preparation method according to claim 2, which is characterized in that Linezolid is Linezolid micro mist in step 3),
Linezolid micro mist is added into solution II, 5000~8000rpm of homogeneous speed disperses 5~10min, mixes, and flocculation must suspend
Liquid III.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610202729.6A CN105853351B (en) | 2016-03-31 | 2016-03-31 | Linezolid oral administration mixed suspension and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610202729.6A CN105853351B (en) | 2016-03-31 | 2016-03-31 | Linezolid oral administration mixed suspension and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105853351A CN105853351A (en) | 2016-08-17 |
| CN105853351B true CN105853351B (en) | 2019-02-22 |
Family
ID=56628014
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610202729.6A Active CN105853351B (en) | 2016-03-31 | 2016-03-31 | Linezolid oral administration mixed suspension and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105853351B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107595782A (en) * | 2017-05-18 | 2018-01-19 | 广州大光制药有限公司 | A kind of Linezolid dry suspensoid agent and preparation method thereof |
| CN109893503A (en) * | 2017-12-11 | 2019-06-18 | 武汉武药科技有限公司 | A kind of Ai Qubo pa oral administration mixed suspension and preparation method thereof |
| CN110393702A (en) * | 2019-08-21 | 2019-11-01 | 苏州二叶制药有限公司 | Oral Dry Suspensions and preparation method thereof containing Linezolid |
| CN111728944B (en) * | 2020-06-28 | 2022-04-01 | 山东达因海洋生物制药股份有限公司 | Linezolid dry suspension and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102973500A (en) * | 2012-12-25 | 2013-03-20 | 江苏吴中苏药医药开发有限责任公司 | Linezolid liquid preparation and preparation method thereof |
| CN104784113A (en) * | 2015-04-30 | 2015-07-22 | 成都国弘医药有限公司 | Linezolid-containing composition and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040191326A1 (en) * | 2003-03-31 | 2004-09-30 | Reo Joseph P. | Taste-masking vehicle for coated oxazolidinone particles |
-
2016
- 2016-03-31 CN CN201610202729.6A patent/CN105853351B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102973500A (en) * | 2012-12-25 | 2013-03-20 | 江苏吴中苏药医药开发有限责任公司 | Linezolid liquid preparation and preparation method thereof |
| CN104784113A (en) * | 2015-04-30 | 2015-07-22 | 成都国弘医药有限公司 | Linezolid-containing composition and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021132;PHARMACIA AND UPJOHN;《Drugs@FDA: FDA Approved Drug Products》;20000418 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105853351A (en) | 2016-08-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105853351B (en) | Linezolid oral administration mixed suspension and preparation method thereof | |
| CN114126596A (en) | Ketamine formulations for subcutaneous injection | |
| KR20120030561A (en) | Injectable formulations containing asenapine and method of treatment using same | |
| BR112015030268B1 (en) | PHARMACEUTICAL COMPOSITION | |
| CN109893503A (en) | A kind of Ai Qubo pa oral administration mixed suspension and preparation method thereof | |
| CN101406455B (en) | Strychnine composite phospholipid liposome, and preparation method thereof and use in pharmacy | |
| US11447456B1 (en) | Crystalline form of lamotrigine hydrate, method for preparing the same and composition comprising the same | |
| CN118290502A (en) | Erigeron breviscapus-huperzine A co-amorphous substance with synergistic antioxidation effect and preparation method thereof | |
| CN102481287A (en) | Pharmaceutical composition of temozolomide comprising vitamin c or vitamin c derivative and preparation method thereof | |
| CN103159787A (en) | Preparation method for high-purity sterilized cefotiam hydrochloride and pharmaceutical composition containing cefotiam hydrochloride | |
| CN102335114B (en) | Stable ibuprofen arginine injection and preparation method thereof | |
| US20230330100A1 (en) | Taste-masking oral formulations of fasudil | |
| CN102688183B (en) | A kind of stable moxifloxacin hydrochloride injection | |
| BRPI0613139A2 (en) | Indibulin tubulin inhibitor pharmaceutical formulation for oral administration with improved pharmacokinetic properties, and process for its manufacture | |
| Gao et al. | Antibacterial performance of tetracycline-active drugs based on ionic liquids | |
| EP2896625A1 (en) | Cocrystal of piperacillin sodium and sulbactam sodium and preparation method thereof, as well as pharmaceutical compositions containing same and uses thereof | |
| CN104844624B (en) | A kind of cefoperazone sodium sulbactam sodium eutectic and composition and method of making the same | |
| CN103655460B (en) | Injection medicinal composition containing aztreonam, as well as preparation method and application thereof | |
| US20040191326A1 (en) | Taste-masking vehicle for coated oxazolidinone particles | |
| CN110003195A (en) | Lurasidone crystal and preparation method thereof and the application in injection delivery systems | |
| CN102258507A (en) | Ibuprofen-containing pharmaceutical composition and its preparation method and application | |
| Zinjad et al. | Solubility Enhancment of Azithromycin by Solid Dispersion Method by using Polymer PVP K 90 | |
| CN108047253A (en) | A kind of Ceftriaxone Sodium crystal-form compound | |
| CN103232476B (en) | A kind of antimicrobial compounds | |
| CN104257618B (en) | Orally disintegrating tablet containing faropenem sodium and preparation method of orally disintegrating tablet |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |