CN111991354A - Compound amoxicillin powder and preparation method thereof - Google Patents
Compound amoxicillin powder and preparation method thereof Download PDFInfo
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- CN111991354A CN111991354A CN201911186228.3A CN201911186228A CN111991354A CN 111991354 A CN111991354 A CN 111991354A CN 201911186228 A CN201911186228 A CN 201911186228A CN 111991354 A CN111991354 A CN 111991354A
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- amoxicillin
- compound
- powder
- sucrose
- amoxicillin powder
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- 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
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- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Abstract
The invention relates to the technical field of medicines, in particular to compound amoxicillin powder and a preparation method thereof; the percentage composition is as follows: 10% of amoxicillin trihydrate (calculated by amoxicillin), 2.5% of potassium clavulanate (calculated by clavulanic acid), 2-30% of strong base and weak acid salt buffer, 5-20% of hygroscopic agent and 100% of anhydrous sugar or sucrose; the stability of the compound amoxicillin powder in the acid solution is improved by using the buffer pair technology: under the concentration of 1500ppm calculated by amoxicillin, the compound amoxicillin powder is dissolved in the components of the artificial chicken liquid (PH3.0) with the temperature of 37 ℃ and is stable within 2 h; thereby ensuring the stability of the product to gastric juice and the treatment effect of the compound amoxicillin powder; by adopting calcium chloride as a stabilizer, the water-absorbing and moisture-absorbing agent has the moisture-absorbing function to keep the stability of the product, and the stability of the clavulanic acid is obviously improved after long-term storage (25 +/-2 ℃ and RH 60% +/-10%) for 6 months.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to compound amoxicillin powder and a preparation method thereof.
Background
Amoxicillin (also known as amoxicillin or amoxicillin) is a commonly used oral broad-spectrum beta-lactam antibiotic, has a bacteriolytic effect and is mainly used for treating bacterial infection caused by susceptible microorganisms. The amoxicillin is white powder, is one of oral semi-synthetic penicillins with wider application, and can be prepared into capsules, tablets, granules, dispersible tablets and the like, and can effectively weaken the drug resistance of germs when being combined with potassium clavulanate.
But the stability of the potassium clavulanate is poor, the treatment effect of diseases is influenced, and the wide application of the preparation in clinics is limited. At present, the compound amoxicillin powder products on the market are relatively few and have good and irregular quality.
Disclosure of Invention
The purpose of the invention is: provides a compound amoxicillin powder with high stability and a preparation method thereof.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
the compound amoxicillin powder comprises the following components in percentage by weight: 10% of amoxicillin trihydrate (calculated by amoxicillin), 2.5% of potassium clavulanate (calculated by clavulanic acid), 2-30% of strong base and weak acid salt buffer, 5-20% of hygroscopic agent and 100% of anhydrous sugar or sucrose.
Further, the strong alkali and weak acid salt buffer pair is sodium carbonate/sodium bicarbonate.
Furthermore, the addition amount of the strong alkali weak acid salt buffer to the selected sodium carbonate is 1-15%, and the addition amount of the sodium bicarbonate is 1-15%.
Further, the mass ratio of the sodium carbonate to the sodium bicarbonate is (10:1) - (1: 10).
Further, the mass ratio of the sodium carbonate to the sodium bicarbonate is 1: 1.
Further, the addition amounts of the sodium carbonate and the sodium bicarbonate are 5% respectively.
Further, the moisture absorbent is one of calcium chloride, magnesium sulfate, calcium sulfate and anhydrous sodium sulfate.
A preparation method of compound amoxicillin powder comprises the following steps:
(1) pulverizing anhydrous sugar or sucrose respectively, and sieving;
(2) sequentially adding full sodium carbonate, sodium bicarbonate, calcium chloride, and the raw materials of amoxicillin and clavulanate potassium, and half anhydrous sugar or sucrose, and mixing for 20-40 min;
(3) adding half amount of anhydrous sugar or sucrose, and mixing for 40-80 min.
Further, the anhydrous sugar or the sucrose in the step (1) are respectively crushed and then sieved by a 80-mesh sieve.
The technical scheme adopted by the invention has the beneficial effects that:
the stability of the compound amoxicillin powder in the acid solution is improved and stabilized by using a buffer pair technology: under the concentration of 1500ppm calculated by amoxicillin, the compound amoxicillin powder is dissolved in the components of the artificial chicken liquid (PH3.0) with the temperature of 37 ℃ and is stable within 2 h; thereby ensuring the stability of the product to gastric juice and the treatment effect of the compound amoxicillin powder;
in the invention, calcium chloride is adopted as a stabilizer, so that the product stability is kept due to the moisture absorption function, and the stability of the clavulanic acid is obviously improved after long-term storage (25 ℃, RH 60%) for 6 months.
Detailed Description
In order to make the aforementioned objects, features and advantages of the present invention comprehensible, the present invention shall be described in detail with reference to the accompanying drawings.
First, reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one implementation of the invention. The appearances of the phrase "in one preferred embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.
The compound amoxicillin powder comprises the following components in percentage by weight: 10% of amoxicillin trihydrate (calculated by amoxicillin), 2.5% of potassium clavulanate (calculated by clavulanic acid), 2-30% of strong base and weak acid salt buffer pair, 5-20% of hygroscopic agent, 100% of anhydrous sugar or sucrose, 1-15% of sodium carbonate/sodium bicarbonate as the strong base and weak acid salt buffer pair, 1-15% of sodium carbonate as the strong base and weak acid salt buffer pair, and 1-15% of sodium bicarbonate as the sodium carbonate and sodium bicarbonate with the preferred mass ratio of (10:1) - (1:10), 1:1 of sodium carbonate and sodium bicarbonate, and 5% of ammonium carbonate and sodium bicarbonate respectively.
Wherein the hygroscopic agent is one of calcium chloride, magnesium sulfate, calcium sulfate and anhydrous sodium sulfate.
A preparation method of compound amoxicillin powder comprises the following steps:
(1) respectively crushing anhydrous sugar or sucrose, and respectively sieving the crushed anhydrous sugar or sucrose with a 80-mesh sieve;
(2) sequentially adding full sodium carbonate, sodium bicarbonate, calcium chloride, and the raw materials of amoxicillin and clavulanate potassium, and half anhydrous sugar or sucrose, and mixing for 20-40 min;
(3) adding half amount of anhydrous sugar or sucrose, and mixing for 40-80 min.
Example 1
The compound amoxicillin powder comprises the following components in percentage by weight: 10% of amoxicillin trihydrate (calculated by amoxicillin), 2.5% of potassium clavulanate (calculated by clavulanic acid), 5% of sodium carbonate, 5% of sodium bicarbonate, 10% of calcium chloride and anhydrous sugar which are added to 100%.
The preparation method of the compound amoxicillin powder comprises the following steps:
(1) respectively crushing anhydrous sugar, and sieving with a 80-mesh sieve;
(2) sequentially adding full sodium carbonate, sodium bicarbonate, calcium chloride, and the raw materials of amoxicillin and clavulanate potassium, full and half anhydrous sugar, and mixing for 40 min;
(3) half the amount of anhydrous sugar was added and mixed for 60 min.
COMPARATIVE EXAMPLE 1 (Weak acid salt buffer pair without strengthening base)
The compound amoxicillin powder comprises the following components in percentage by weight: 10% of amoxicillin trihydrate (calculated by amoxicillin), 2.5% of potassium clavulanate (calculated by clavulanic acid), 10% of calcium chloride and anhydrous sugar added to 100%.
The preparation method of the compound amoxicillin powder comprises the following steps:
(1) respectively crushing anhydrous sugar, and sieving with a 80-mesh sieve;
(2) sequentially adding the total calcium chloride, the total amoxicillin and potassium clavulanate as raw materials, and the half anhydrous sugar in sequence, and mixing for 40 min;
(3) half the amount of anhydrous sugar was added and mixed for 60 min.
Comparative example 2 (without addition of moisture absorbent)
The compound amoxicillin powder comprises the following components in percentage by weight: 10% of amoxicillin trihydrate (calculated by amoxicillin), 2.5% of potassium clavulanate (calculated by clavulanic acid), 5% of sodium carbonate, 5% of sodium bicarbonate and 100% of anhydrous sugar.
The preparation method of the compound amoxicillin powder comprises the following steps:
(1) respectively crushing anhydrous sodium sulfate and anhydrous sugar, and sieving with a 80-mesh sieve;
(2) sequentially adding full amount of sodium carbonate, sodium bicarbonate and half amount of anhydrous sugar and mixing for 40 min;
(3) half the amount of anhydrous sugar was added and mixed for 60 min.
Example 1 is a preferred embodiment of the present invention.
And (3) performance testing:
1. stability of acid solution
The stability of the amoxicillin compound powder dissolved in the components amoxicillin and clavulanic acid of 37 ℃ artificial chicken broth (pH3.0) was tested at a concentration of 1500ppm, calculated respectively for amoxicillin (example 1 and comparative example 1), and is shown in Table 1.
TABLE 1
2. Storage stability (Long term data for potassium clavulanate)
By comparing the amoxicillin compound powder of example 1 with the amoxicillin compound powder of comparative example 2, the influence of the hygroscopic agent on the storage stability of the amoxicillin compound powder is shown in the long-term data of potassium clavulanate in Table 2.
TABLE 2
As can be seen from tables 1 and 2, the stability of the compound amoxicillin powder in the acid solution is improved and stabilized by using the buffer pair technology in the invention: dissolving compound amoxicillin powder in a solution of artificial chicken liquid (PH3.0) at 37 deg.C under the concentration of 1500ppm calculated by amoxicillin, wherein the amoxicillin and clavulanic acid are stable within 2 h; thereby ensuring the stability of the product to gastric juice and the treatment effect of the compound amoxicillin powder; in the invention, calcium chloride is adopted as a stabilizer, so that the product stability is kept due to the moisture absorption function, and the stability of the clavulanic acid is obviously improved after long-term storage (25 ℃, RH 60%) for 6 months.
3. The effect of the hygroscopic agent on the content of clavulanic acid in the compound amoxicillin powder is shown in table 3.
The influence of calcium chloride on the content of clavulanic acid (the addition amount of other components in the formula is the same as that in example 1) is analyzed in combination with the acceleration of two samples for preparation for half a month, and the content reduction value is used as an evaluation index because the initial concentrations of the two samples are different.
TABLE 3
| The amount of calcium chloride added | Reduction value (%) |
| 0 | 29.72 |
| 2.7 | 12.05 |
| 3.3 | 18.4 |
| 4.5 | 17.80 |
| 9 | 8.02 |
| 10 | 3.79 |
| 20 | 3.2 |
As can be seen from table 3, the decrease in the amount of clavulanic acid gradually decreased with the addition of calcium chloride, and when the amount of addition reached 10%, the decrease in the amount of clavulanic acid decreased significantly, and when the amount of addition increased to 20%, the decrease in the amount of clavulanic acid was less significant than the decrease in the amount of addition of 10%, and the production cost increased rather much, so that the amount of addition of calcium chloride was preferably 10% in consideration of the production cost and the stability of clavulanic acid.
The inventor of the invention also carries out experimental verification on the dosage except the end point value in the invention, and the conclusion is that: the amounts other than the above-mentioned limits, the stability of the acid solution and the storage stability are inferior to those of the present invention.
In light of the foregoing description of the preferred embodiment of the present invention, many modifications and variations will be apparent to those skilled in the art without departing from the spirit and scope of the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention. The technical scope of the present invention is not limited to the contents of the specification, and must be determined according to the scope of the claims.
Claims (9)
1. The compound amoxicillin powder is characterized in that: the percentage composition is as follows: 10% of amoxicillin trihydrate (calculated by amoxicillin), 2.5% of potassium clavulanate (calculated by clavulanic acid), 2-30% of strong base and weak acid salt buffer, 5-20% of hygroscopic agent and 100% of anhydrous sugar or sucrose.
2. The compound amoxicillin powder of claim 1, characterized in that: the strong base weak acid salt buffer pair is sodium carbonate/sodium bicarbonate.
3. The compound amoxicillin powder of claim 2, characterized in that: the addition amount of the strong alkali weak acid salt buffer to the selected sodium carbonate is 1-15%, and the addition amount of the sodium bicarbonate is 1-15%.
4. The compound amoxicillin powder of claim 3, characterized in that: the mass ratio of the sodium carbonate to the sodium bicarbonate is (10:1) - (1: 10).
5. The compound amoxicillin powder of claim 4, characterized in that: the mass ratio of the sodium carbonate to the sodium bicarbonate is 1: 1.
6. The compound amoxicillin powder of claim 5, characterized in that: the addition amounts of the sodium carbonate and the sodium bicarbonate are respectively 5%.
7. The compound amoxicillin powder of claim 1, characterized in that: the hygroscopic agent is one of calcium chloride, magnesium sulfate, calcium sulfate and anhydrous sodium sulfate.
8. The method for preparing the compound amoxicillin powder as claimed in any one of claims 1 to 7, characterized in that: the preparation method comprises the following steps:
(1) pulverizing anhydrous sugar or sucrose respectively, and sieving;
(2) sequentially adding full sodium carbonate, sodium bicarbonate, calcium chloride, and the raw materials of amoxicillin and clavulanate potassium, and half anhydrous sugar or sucrose, and mixing for 20-40 min;
(3) adding half amount of anhydrous sugar or sucrose, and mixing for 40-80 min.
9. The preparation method of the compound amoxicillin powder as claimed in claim 6, characterized in that: and (2) respectively crushing anhydrous sugar or sucrose in the step (1) and then sieving the crushed anhydrous sugar or sucrose with a 80-mesh sieve.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201911186228.3A CN111991354A (en) | 2019-11-28 | 2019-11-28 | Compound amoxicillin powder and preparation method thereof |
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| CN201911186228.3A CN111991354A (en) | 2019-11-28 | 2019-11-28 | Compound amoxicillin powder and preparation method thereof |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105919941A (en) * | 2016-05-17 | 2016-09-07 | 湖南泰谷生物兽药有限公司 | Composition containing amoxicillin and potassium clavulanate, and preparation method thereof |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105919941A (en) * | 2016-05-17 | 2016-09-07 | 湖南泰谷生物兽药有限公司 | Composition containing amoxicillin and potassium clavulanate, and preparation method thereof |
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