CN114668724A - Amoxicillin and clavulanate potassium dry suspension and preparation method thereof - Google Patents
Amoxicillin and clavulanate potassium dry suspension and preparation method thereof Download PDFInfo
- Publication number
- CN114668724A CN114668724A CN202011549387.8A CN202011549387A CN114668724A CN 114668724 A CN114668724 A CN 114668724A CN 202011549387 A CN202011549387 A CN 202011549387A CN 114668724 A CN114668724 A CN 114668724A
- Authority
- CN
- China
- Prior art keywords
- amoxicillin
- clavulanate
- potassium
- dry suspension
- agent
- 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.)
- Granted
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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/424—Oxazoles condensed with heterocyclic ring systems, e.g. clavulanic acid
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
-
- 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)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the technical field of pharmaceutical preparations, and discloses a prescription composition of an amoxicillin and potassium clavulanate dry suspension and a preparation method thereof. The amoxicillin and clavulanate potassium dry suspension prepared by the invention has high dissolution rate and high stability.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to a prescription composition of an amoxicillin and clavulanate potassium dry suspension and a preparation process thereof.
Background
The chemical name of amoxicillin is: (2S, 5R, 6R) -3, 3-dimethyl-6- [ (R) - (-) -2-amino-2- (4-hydroxyphenyl) acetamido ] -7-oxo-4-thia-1-azabicyclo [3.2.0] heptane-2-carboxylic acid trihydrate, having the chemical structure:
the chemical name of the potassium clavulanate is as follows: (Z) - (2R,5R) -3- (2-hydroxyethyl) -7-oxo-4-oxa-1-azabicyclo [3.2.0] heptane-2-carboxylic acid potassium salt having the chemical structure:
amoxicillin is a white or off-white crystalline powder, slightly soluble in water, almost insoluble in ethanol, and soluble in dissolution media at various pH values (37 ℃): pH 1.2: 30.7mg/ml, pH 4.0: 3.8mg/ml, pH 6.8: 4.9mg/ml, water: 3.6mg/ml, the amoxicillin solubility is seen to be in a descending trend along with the increase of the pH value of the solution, and the amoxicillin solubility is basically kept unchanged after the pH value of the solution is increased to 4.0.
The potassium clavulanate is white to yellowish crystalline powder and is slightly smelly; very easy to draw moisture, very easy to dissolve in water, very soluble in methanol, slightly soluble in ethanol, insoluble in ether, solubility in dissolution media at various pH values (37 ℃): pH 1.2: 2.5g/ml, pH 4.0: 2.5g/ml, pH 6.8: 2.5g/ml, water: 2.5g/ml, without pH dependence.
A dry suspension of amoxicillin and clavulanate potassium for use in the short-term treatment of infections suspected to be caused by amoxicillin-resistant bacteria producing beta-lactamase. Bacterial resistance is primarily due to the production of beta-lactamase enzymes by bacteria, which destroy antibiotics before they act on pathogenic bacteria.
Amoxicillin is a semi-synthetic broad-spectrum antibiotic, which acts on many gram-positive and gram-negative bacteria. However, beta-lactamase may reduce the effect of amoxicillin and therefore the spectrum of bacteria in which amoxicillin acts does not include beta-lactamase producing bacteria. Clavulanic acid is a beta-lactam, has a structure similar to that of penicillin, and has an inhibiting effect on common beta-lactamase of penicillin-resistant and cephalosporin existing in microorganisms. In particular, the clavulanic acid has stronger inhibiting effect on the beta-lactamase which has important clinical significance, is mediated by plasmid and can cause cross drug resistance. Therefore, the existence of the clavulanic acid can protect the amoxicillin from the degradation of the beta-lactamase, thereby expanding the antibacterial spectrum of the amoxicillin. These include many bacteria that are normally resistant to amoxicillin and other penicillins and cephalosporins. Therefore, the product has obvious broad-spectrum antibacterial effect and is a beta-lactamase inhibitor.
Currently, an amoxicillin and clavulanate potassium compound preparation is mainly an oral solid preparation, and comprises tablets, capsules and dry suspensions. Because the tablet and the capsule are not beneficial to children, old people and dysphagia patients, the dry suspension has strong clinical compliance, can be administrated in divided doses, is convenient to take and has high dissolution rate. However, the stability of amoxicillin and potassium clavulanate in acid-base media is poor, and adverse reactions are easy to occur after patients take the amoxicillin and potassium clavulanate, so that the difficulty of the development of the preparation is to ensure the quality stability of the product.
Patent CN103127099A discloses an amoxicillin and clavulanate potassium dry suspension (4:1) and a production process thereof, which is prepared by mixing amoxicillin, clavulanate potassium, hydroxypropyl methylcellulose and the like, but the preparation process is complex, the clavulanate potassium and phospholipid are dissolved in chloroform, silicon dioxide is added, stirring is carried out, the chloroform is evaporated to dryness under reduced pressure at the temperature of below 40 ℃, and then the mixture is sieved and mixed with other materials to prepare the amoxicillin and clavulanate potassium dry suspension.
The patent CN110859801A discloses an amoxicillin and clavulanate potassium dry suspension and a preparation method thereof, wherein the amoxicillin and clavulanate potassium dry suspension is composed of the following raw and auxiliary materials in parts by weight: 16-18 parts of amoxicillin, 10-12 parts of amoxicillin and clavulanate potassium mixed powder, 70-85 parts of sucrose, 1-9 parts of xanthan gum, 2-10 parts of hydroxypropyl methylcellulose, 2-3 parts of aspartame, 1-12 parts of silicon dioxide and 1-2 parts of fruit milk essence; wherein the mass ratio of amoxicillin to potassium clavulanate in the amoxicillin and potassium clavulanate mixed powder is 2: 1. The product is directly filled with powder. However, this patent only compares the dissolution in buffer solution of pH5.0 and the drug is about 1.2 g/bag in a single dose weight, which is costly.
Disclosure of Invention
Based on the defects of the prior art, the invention provides a prescription of an amoxicillin and clavulanate potassium dry suspension and a preparation method thereof.
The amoxicillin and clavulanate potassium dry suspension contains the following components: amoxicillin, potassium clavulanate, flavoring agent, diluent, thickening agent, stabilizing agent, suspending agent, pH regulator and aromatic.
Specifically, the amoxicillin and clavulanate potassium dry suspension comprises the following components:
30-60% of amoxicillin, 5-15% of potassium clavulanate, 1-5% of flavoring agent, 3-10% of diluent, 1-5% of thickening agent, 10-25% of stabilizer, 10-30% of suspending agent, 0.1-0.5% of pH regulator and 0.01-10% of aromatic;
preferably, the amoxicillin and clavulanate potassium dry suspension contains the following components:
42-56% of amoxicillin, 6-8% of potassium clavulanate, 2-3% of flavoring agent, 4-6% of diluent, 2-3% of thickening agent, 14-18% of stabilizer, 12-22% of suspending agent, 0.1-0.2% of pH regulator and 0.02-10% of aromatic.
In the amoxicillin and clavulanate potassium dry suspension:
the flavoring agent is one or more selected from aspartame, sucrose, sodium alginate, acacia, gelatin, methylcellulose, and sodium carboxymethylcellulose;
the diluent is selected from one or more of maltodextrin, starch, pregelatinized starch, lactose, microcrystalline cellulose, mannitol, and sorbitol;
the suspending agent is selected from one or more of colloidal silicon dioxide, acacia, sodium alginate, agar, starch slurry, sodium carboxymethylcellulose, and hydroxypropyl cellulose;
the stabilizer is microcrystalline cellulose-sodium carboxymethyl cellulose; the thickener is one or more selected from xanthan gum, sodium alginate, agar and carrageenan;
the pH regulator is one or more selected from succinic acid, citric acid, lactic acid, tartaric acid, fumaric acid, acetic acid, hydrochloric acid, phosphoric acid, and malic acid;
the aromatic is selected from one or more of herba Menthae essence, fructus Citri sinensis essence, Rubi fructus essence, fructus Citri Limoniae essence, and ginger oil essence;
preferably, the flavoring agent is selected from one or more of aspartame, sucrose and sodium alginate;
the diluent is selected from one or more of maltodextrin, starch, lactose and microcrystalline cellulose;
the suspending agent is selected from one or more of colloidal silicon dioxide, Arabic gum and hydroxypropyl cellulose;
the pH regulator is selected from one or more of succinic acid, citric acid, tartaric acid and lactic acid;
the aromatic is a mixture of sweet orange essence and raspberry essence.
Further preferably, the flavoring agent is aspartame;
the diluent is maltodextrin;
the suspending agent is colloidal silicon dioxide;
the pH regulator is succinic acid;
the ratio of the sweet orange essence to the raspberry essence is 1: 0.1-5; more preferably, the ratio of the sweet orange essence to the raspberry essence is 1: 0.5-3.
The invention also provides a preparation process of the amoxicillin and clavulanate potassium dry suspension, which mainly comprises the following steps:
step 1: mixing a pH regulator and a thickening agent, adding a flavoring agent, a diluting agent and a stabilizing agent, and mixing to obtain mixed powder I; mixing amoxicillin, potassium clavulanate and a suspending agent to obtain mixed powder II;
step 2: mixing the mixed powder I and II, adding aromatic, and mixing.
Specifically, the preparation method comprises the following steps:
step 1, drying: xanthan gum, maltodextrin (sieved by a 80-mesh sieve), aspartame, microcrystalline cellulose-sodium carboxymethylcellulose, drying for 4 hours at 105 ℃, and controlling the water content of the auxiliary materials to be less than or equal to 2.0 percent;
step 2, mixing and sieving: the environment temperature is 18-26 ℃, the environment humidity is less than or equal to 35%, succinic acid and xanthan gum are mixed and sieved by a 80-mesh sieve, aspartame is added and mixed and sieved by a 80-mesh sieve, maltodextrin is added and mixed and sieved by a 80-mesh sieve, and microcrystalline cellulose-sodium carboxymethylcellulose is added and mixed and sieved by a 80-mesh sieve to obtain mixed powder I; mixing amoxicillin, potassium clavulanate and colloidal silicon dioxide, and sieving with a 80-mesh sieve to obtain mixed powder II; finally, mixing the mixed powder I and the mixed powder II, sieving the mixture by a 80-mesh sieve, and uniformly mixing the mixture;
step 3, total mixing: uniformly mixing the mixed powder obtained in the step S2 with essence;
step 4, detecting the content of the mixed powder and calculating the theoretical loading
And 5, bottling the mixed powder in multiple doses or filling the mixed powder in a compound bag in a single dose according to production requirements to obtain the powder.
Compared with the prior art, the amoxicillin and clavulanate potassium dry suspension prepared by the invention has similar dissolution curve, particle size distribution and powder properties to those of the original ground product, has better quality stability than the original ground product, has simple and feasible preparation method, is suitable for large-scale production and meets the market demand.
Detailed Description
The present invention is further described with reference to the following examples, which are given for the purpose of illustration only and are not to be construed as limiting the invention.
Example 1
The preparation method comprises the following steps:
1. drying: xanthan gum, maltodextrin (sieved by a 80-mesh sieve firstly), aspartame, microcrystalline cellulose-sodium carboxymethylcellulose,
drying at 105 deg.C for 4 hr, and controlling water content of adjuvant to be less than or equal to 2.0%;
2. mixing and sieving: the environment temperature is 18-26 ℃, the environment humidity is less than or equal to 35%, succinic acid and xanthan gum are mixed and sieved by a 80-mesh sieve, aspartame is added and mixed and sieved by a 80-mesh sieve, maltodextrin is added and mixed and sieved by a 80-mesh sieve, and microcrystalline cellulose-sodium carboxymethylcellulose is added and mixed and sieved by a 80-mesh sieve to obtain mixed powder I; mixing amoxicillin, potassium clavulanate and colloidal silicon dioxide, and sieving with a 80-mesh sieve to obtain mixed powder II; finally, mixing the mixed powder I and the mixed powder II, sieving the mixture by a 80-mesh sieve, and uniformly mixing the mixture;
3. total mixing: uniformly mixing the mixed powder obtained in the step S2 with essence;
4. detecting the content of the mixed powder and calculating the theoretical loading
5. Filling the mixed powder into glass bottles according to 14 doses; loading single dose into aluminum-plastic composite bags.
Example 2
The preparation method comprises the following steps: reference is made to example 1.
Example 3
The preparation method comprises the following steps: reference is made to example 1.
Example 4
The preparation method comprises the following steps: reference is made to example 1.
Example 5
The preparation method comprises the following steps: reference is made to example 1.
Example 6
The preparation method comprises the following steps: reference is made to example 1.
Example 7
The preparation method comprises the following steps: reference is made to example 1.
Example 8
The preparation method comprises the following steps: reference is made to example 1.
Example 9
The preparation method comprises the following steps: reference is made to example 1.
Example 10
The preparation method comprises the following steps: reference is made to example 1.
Example 11
The preparation method comprises the following steps: reference is made to example 1.
Example 12
The preparation method comprises the following steps: reference is made to example 1.
Example 13
The preparation method comprises the following steps: reference is made to example 1.
Example 14
The preparation method comprises the following steps: reference is made to example 1.
Verification of the examples:
quality, particle size distribution and powder property detection
The amoxicillin and clavulanate potassium dry suspension prepared in the embodiment 1-4 is subjected to quality, particle size distribution and powder property detection, and the results are shown in tables 1 and 2.
Table 1: example 1-4 detection results of quality of amoxicillin and clavulanate potassium dry suspension and original drug
Table 2: example 1-4 detection results of quality of amoxicillin and clavulanate potassium dry suspension and original drug
Note 1: the amount of water dissolved in the dissolution medium was 30 minutes, and the limit was 80% of the indicated amount.
According to the detection results, the quality indexes of the products prepared according to the formulas and processes of the embodiments 1-4, such as appearance, particle size distribution, powder properties, product content, dissolution rate, related substances and the like, are consistent with those of the original preparation.
Second, stability survey
To compare the consistency of the product prepared according to the recipe and process of the present invention with the quality of the original research, the present invention conducted accelerated stability studies on three batches of samples (lot numbers: 180501, 180502, 180503, respectively) prepared according to the recipe and process of example 2 and the original research reagent (lot number: T84A, manufacturing company: Glan Schke), and examined the conditions: temperature 30 ℃, relative humidity: 65% +/-5%. The results are shown in tables 3 and 4.
Table 3: accelerated stability test result of amoxicillin and clavulanate potassium dry suspension
Table 4: accelerated stability test result of amoxicillin and clavulanate potassium dry suspension
As can be seen from the table above, the amoxicillin and potassium clavulanate dry suspension and the original ground product obtained in example 2 have substantially no changes in the contents and dissolution rates of amoxicillin and potassium clavulanate under the condition of sample retention acceleration, no obvious changes in related substances and fluorescent substances, and only 0.2% increase in total impurities.
Third, dissolution Curve comparison
Taking the amoxicillin and clavulanate dry suspension (batch number: 180501) of example 2 and the amoxicillin and clavulanate dry suspension (batch number: T84A) of the original research product, referring to the test device of the second method of the four 0931 dissolution test method of the Chinese pharmacopoeia 2015 edition, taking water, hydrochloric acid solution with pH1.2, acetate buffer solution with pH4.5 and phosphate buffer solution with pH6.8 as dissolution media, rotating at 75 revolutions per minute, calculating the cumulative dissolution amount of the drug, and drawing a dissolution curve, the results are shown in tables 5 and 6.
Table 5: 180501 and T84A amoxicillin dissolution curve comparison result
Table 6: 180501 comparison with T84A clavulanate potassium dissolution curve
As can be seen from the dissolution curve data, the dissolution rates of amoxicillin and potassium clavulanate in 15 minutes of the self-prepared product and the original ground product are both more than or equal to 85 percent, so the dissolution behavior of the amoxicillin and potassium clavulanate in vitro is similar to that of the reference preparation.
Claims (10)
1. The amoxicillin and clavulanate potassium dry suspension is characterized by comprising the following components: amoxicillin, potassium clavulanate, flavoring agent, diluent, thickening agent, stabilizing agent, suspending agent, pH regulator and aromatic.
2. The amoxicillin potassium clavulanate dry suspension of claim 1 which comprises the following components:
30-60% of amoxicillin, 5-15% of potassium clavulanate, 1-5% of flavoring agent, 3-10% of diluent, 1-5% of thickening agent, 10-25% of stabilizer, 10-30% of suspending agent, 0.1-0.5% of pH regulator and 0.01-10% of aromatic;
preferably, the amoxicillin and clavulanate potassium dry suspension contains the following components:
42-56% of amoxicillin, 6-8% of clavulanate potassium, 2-3% of flavoring agent, 4-6% of diluent, 2-3% of thickening agent, 14-18% of stabilizing agent, 12-22% of suspending agent, 0.1-0.2% of pH regulator and 0.02-10% of aromatic.
3. The amoxicillin and clavulanate potassium dry suspension as claimed in claim 1 or 2, wherein the flavoring agent is selected from one or more of aspartame, sucrose, sodium alginate, acacia, gelatin, methylcellulose, sodium carboxymethylcellulose; preferably, the flavoring agent is selected from one or more of aspartame, sucrose and sodium alginate.
4. The amoxicillin and clavulanate potassium dry suspension according to claim 1 or 2 wherein the diluent is selected from one or more of maltodextrin, starch, pregelatinized starch, lactose, microcrystalline cellulose, mannitol, sorbitol; preferably, the diluent is selected from one or more of maltodextrin, starch, lactose, and microcrystalline cellulose.
5. The amoxicillin and clavulanate potassium dry suspension as claimed in claim 1 or 2, wherein the suspending agent is selected from one or more of colloidal silicon dioxide, acacia, sodium alginate, agar, starch slurry, sodium carboxymethylcellulose, hydroxypropyl cellulose; preferably, the suspending agent is selected from one or more of colloidal silica, acacia and hydroxypropyl cellulose.
6. The dry suspension of amoxicillin and clavulanate potassium according to claim 1 or 2 wherein the stabilizer is microcrystalline cellulose-sodium carboxymethylcellulose.
7. The amoxicillin and clavulanate potassium dry suspension according to claim 1 or 2, wherein the thickener is selected from one or more of xanthan gum, sodium alginate, agar, carrageenan.
8. The amoxicillin and clavulanate potassium dry suspension according to claim 1 or 2, wherein the pH modifier is selected from one or more of succinic acid, citric acid, lactic acid, tartaric acid, fumaric acid, acetic acid, hydrochloric acid, phosphoric acid, malic acid; preferably, the pH regulator is selected from one or more of succinic acid, citric acid, tartaric acid and lactic acid.
9. The amoxicillin and clavulanate potassium dry suspension as claimed in claim 1 or 2, wherein the flavoring agent is selected from one or more of mint flavor, orange flavor, raspberry flavor, lemon flavor, ginger oil flavor; preferably, the aromatic is a mixture of sweet orange essence and raspberry essence; further preferably, the ratio of the sweet orange essence to the raspberry essence is 1: 0.1-5; preferably, the ratio of the sweet orange essence to the raspberry essence is 1: 0.5-3.
10. The amoxicillin and potassium clavulanate dry suspension as claimed in claim 1 or 2, wherein the preparation process of the amoxicillin and potassium clavulanate dry suspension mainly comprises the following steps:
step 1: mixing a pH regulator and a thickening agent, adding a flavoring agent, a diluting agent and a stabilizing agent, and mixing to obtain mixed powder I; mixing amoxicillin, potassium clavulanate and a suspending agent to obtain mixed powder II;
step 2: mixing the mixed powder I and II, adding aromatic, and mixing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011549387.8A CN114668724B (en) | 2020-12-24 | 2020-12-24 | Amoxicillin and clavulanate potassium dry suspension and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011549387.8A CN114668724B (en) | 2020-12-24 | 2020-12-24 | Amoxicillin and clavulanate potassium dry suspension and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114668724A true CN114668724A (en) | 2022-06-28 |
| CN114668724B CN114668724B (en) | 2023-08-22 |
Family
ID=82070839
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011549387.8A Active CN114668724B (en) | 2020-12-24 | 2020-12-24 | Amoxicillin and clavulanate potassium dry suspension and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114668724B (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004110441A1 (en) * | 2003-06-16 | 2004-12-23 | Glaxo Group Limited | Pharmaceutical formulations comprising amoxicillin and clavulanate |
| US6977086B1 (en) * | 1999-08-20 | 2005-12-20 | Laboratorie Glaxosmithkline S.A.S. | Pharmaceutical formulation comprising amoxycillin and clavulanate |
| CN1809348A (en) * | 2003-06-16 | 2006-07-26 | 葛兰素集团有限公司 | Pharmaceutical formulations comprising amoxicillin and clavulanante |
| CN101632661A (en) * | 2009-05-25 | 2010-01-27 | 北京诚创康韵医药科技有限公司 | Compound amoxicillin slow release dry suspension composition and preparation method thereof |
| CN102614174A (en) * | 2012-02-24 | 2012-08-01 | 南京臣功制药股份有限公司 | Dry suspension containing amoxicillin and potassium clavulanate |
| CN103961351A (en) * | 2014-05-06 | 2014-08-06 | 康田制药(中山)有限公司 | Preparation method of amoxicillin and clavulanate potassium tablets |
-
2020
- 2020-12-24 CN CN202011549387.8A patent/CN114668724B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6977086B1 (en) * | 1999-08-20 | 2005-12-20 | Laboratorie Glaxosmithkline S.A.S. | Pharmaceutical formulation comprising amoxycillin and clavulanate |
| WO2004110441A1 (en) * | 2003-06-16 | 2004-12-23 | Glaxo Group Limited | Pharmaceutical formulations comprising amoxicillin and clavulanate |
| CN1809348A (en) * | 2003-06-16 | 2006-07-26 | 葛兰素集团有限公司 | Pharmaceutical formulations comprising amoxicillin and clavulanante |
| CN101632661A (en) * | 2009-05-25 | 2010-01-27 | 北京诚创康韵医药科技有限公司 | Compound amoxicillin slow release dry suspension composition and preparation method thereof |
| CN102614174A (en) * | 2012-02-24 | 2012-08-01 | 南京臣功制药股份有限公司 | Dry suspension containing amoxicillin and potassium clavulanate |
| CN103961351A (en) * | 2014-05-06 | 2014-08-06 | 康田制药(中山)有限公司 | Preparation method of amoxicillin and clavulanate potassium tablets |
Non-Patent Citations (2)
| Title |
|---|
| 姚静 等: "《药物辅料应用指南》", 31 August 2011 * |
| 钟银杭: "复方阿莫西林干混悬剂的制备与稳定性考察", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114668724B (en) | 2023-08-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101816635B (en) | Cephalosporin suspension granule and preparation method thereof | |
| CN103349646B (en) | A kind of pharmaceutical composition of cefaclor granule, its preparation method and application | |
| JPH11512398A (en) | Pharmaceutical prescription | |
| CN103417512B (en) | A kind of Biomox and preparation method thereof | |
| CN103524533B (en) | A kind of cefprozil compound, its dispersible tablet, dry suspensoid and preparation method | |
| CN103330685B (en) | Cefaclor granule and preparation method thereof | |
| CN102875573A (en) | Cefixime compound and pharmaceutical composition thereof | |
| CN114668724B (en) | Amoxicillin and clavulanate potassium dry suspension and preparation method thereof | |
| CN109248150B (en) | Amoxicillin and clavulanate potassium preparation and preparation method thereof | |
| CN113476406A (en) | Veterinary compound amoxicillin powder and preparation process thereof | |
| CN117379378A (en) | Compound amoxicillin soluble powder for livestock and preparation process thereof | |
| CN103145733B (en) | Amoxicillin compound and pharmaceutical composition of amoxicillin compound and potassium clavulanate | |
| CN104688698B (en) | A kind of Cefditoren pivoxil Cephalosporins tablet | |
| CN105147599B (en) | Netilmicin sulfate injection and preparation method | |
| CN103622916B (en) | Cefixime dry suspension and preparation method thereof | |
| CN101225093B (en) | Aminoglycoside derivatives | |
| CN105496984B (en) | A kind of Cefixime Capsules and preparation method thereof that quality is stable | |
| CN102327270A (en) | Beta-lactam compound antibiotic composition | |
| CN103405387B (en) | A kind of new Cefixime suspension and preparation method thereof | |
| CN110859801A (en) | Amoxicillin potassium clavulanate dry suspension and preparation method thereof | |
| CN110327284B (en) | Cefodizime sodium for injection and preparation method thereof | |
| CN1115147C (en) | Improved method for preparing potassim clavulanate | |
| CN111150709B (en) | Methylprednisolone sodium succinate for injection and preparation method thereof | |
| CN113679672A (en) | Preparation method of high-water-solubility amoxicillin soluble powder | |
| CN111671912A (en) | Composition containing cobamamide, freeze-dried powder, preparation method thereof and injection medicine |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |