CN116440158B - Iron sucrose composition, and preparation method and application thereof - Google Patents
Iron sucrose composition, and preparation method and application thereof Download PDFInfo
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- CN116440158B CN116440158B CN202310314591.9A CN202310314591A CN116440158B CN 116440158 B CN116440158 B CN 116440158B CN 202310314591 A CN202310314591 A CN 202310314591A CN 116440158 B CN116440158 B CN 116440158B
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- FWZTTZUKDVJDCM-CEJAUHOTSA-M disodium;(2r,3r,4s,5s,6r)-2-[(2s,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol;iron(3+);oxygen(2-);hydroxide;trihydrate Chemical compound O.O.O.[OH-].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[Na+].[Na+].[Fe+3].[Fe+3].[Fe+3].[Fe+3].[Fe+3].O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 FWZTTZUKDVJDCM-CEJAUHOTSA-M 0.000 title claims abstract description 136
- 229940032961 iron sucrose Drugs 0.000 title claims abstract description 136
- 239000000203 mixture Substances 0.000 title claims abstract description 72
- 238000002360 preparation method Methods 0.000 title claims abstract description 47
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 123
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 108
- 238000000034 method Methods 0.000 claims abstract description 41
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 25
- 239000001301 oxygen Substances 0.000 claims abstract description 25
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 25
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 118
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 102
- 239000000243 solution Substances 0.000 claims description 92
- 229910052742 iron Inorganic materials 0.000 claims description 59
- 230000001954 sterilising effect Effects 0.000 claims description 52
- 239000003814 drug Substances 0.000 claims description 49
- 239000007788 liquid Substances 0.000 claims description 49
- 238000003756 stirring Methods 0.000 claims description 43
- 238000002347 injection Methods 0.000 claims description 41
- 239000007924 injection Substances 0.000 claims description 41
- 229940090044 injection Drugs 0.000 claims description 40
- 238000004659 sterilization and disinfection Methods 0.000 claims description 40
- 239000008215 water for injection Substances 0.000 claims description 33
- 230000001276 controlling effect Effects 0.000 claims description 32
- 229940097452 iron sucrose injection Drugs 0.000 claims description 32
- 238000001914 filtration Methods 0.000 claims description 21
- 239000002994 raw material Substances 0.000 claims description 19
- 239000011521 glass Substances 0.000 claims description 16
- 238000001514 detection method Methods 0.000 claims description 14
- 239000000463 material Substances 0.000 claims description 14
- 230000001105 regulatory effect Effects 0.000 claims description 14
- 238000007689 inspection Methods 0.000 claims description 13
- 238000004806 packaging method and process Methods 0.000 claims description 13
- 238000012805 post-processing Methods 0.000 claims 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 abstract description 26
- 239000003381 stabilizer Substances 0.000 abstract description 20
- 239000012535 impurity Substances 0.000 abstract description 8
- 239000000047 product Substances 0.000 description 31
- 239000005720 sucrose Substances 0.000 description 30
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 29
- 229930006000 Sucrose Natural products 0.000 description 29
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 15
- 239000011148 porous material Substances 0.000 description 15
- 238000002156 mixing Methods 0.000 description 13
- 238000007789 sealing Methods 0.000 description 6
- 239000003708 ampul Substances 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 5
- 238000011049 filling Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 238000005273 aeration Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960004887 ferric hydroxide Drugs 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- IEECXTSVVFWGSE-UHFFFAOYSA-M iron(3+);oxygen(2-);hydroxide Chemical compound [OH-].[O-2].[Fe+3] IEECXTSVVFWGSE-UHFFFAOYSA-M 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 241001391944 Commicarpus scandens Species 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 238000009924 canning Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000008824 ferric saccharate Nutrition 0.000 description 1
- 239000011788 ferric saccharate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- XRDYWGSODBNAIE-BQGRAUOOSA-K iron(3+);(2r,3s,4s,5s)-2,3,4,5,6-pentahydroxy-6-oxohexanoate Chemical compound [Fe+3].OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O XRDYWGSODBNAIE-BQGRAUOOSA-K 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 229940035081 venofer Drugs 0.000 description 1
- 238000004832 voltammetry Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7016—Disaccharides, e.g. lactose, lactulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/26—Iron; Compounds 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
- A61K47/02—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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Dermatology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an iron sucrose composition, a preparation method and application thereof. Specifically disclosed is an iron sucrose composition comprising iron sucrose, a stabilizer, and water; the stabilizer is selected from 1,2 or 3 of dissolved oxygen, ozone and hydrogen peroxide. The iron sucrose composition provided by the invention can be used for preparing iron sucrose, and the process has few impurities and wide application prospect.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to an iron sucrose composition, a preparation method and application thereof.
Background
The ferric saccharate injection is a polynuclear ferric hydroxide (III) -sucrose complex solution and is clinically used for treating patients with poor oral iron agent effect and needs intravenous iron agent treatment. The core surface of polynuclear ferric hydroxide (III) is surrounded by a large number of non-covalent binding sucrose molecules to form a macromolecular structure compound, the number average molecular weight of which is not less than 24000Da and the weight average molecular weight of which is 34000-60000Da.
The product was originally developed by the company vifor Switzerland (original research), approved in the European Union in 1998, and the original research product was marketed in China with the approval import, trade name Venofer (velafu), approval specification 5ml:100mg iron and 1.6g sucrose.
Iron sucrose injections are unstable at high temperatures and produce ferrous impurities, which, although being a component of hemoglobin, lack can cause anemia, but excessive intake is also harmful to the body. The USP-NF2021 sucrose iron injection item prescribes that the ferrous iron content is not more than 0.4%.
The iron sucrose injection belongs to a small-volume injection, and the sterilization process of the injection is a damp heat sterilization process, but the sterilization process needs a high-temperature link, so that the iron sucrose injection is easy to increase ferrous impurities, thereby causing unqualified products.
The ferrous content of the initial raw materials in the original grinding product needs to be controlled to be very low (such as less than 0.1 percent) so as to achieve the control of the ferrous content of the final product to meet the requirement. However, the control of the ferrous iron content of the initial raw material is very low, the technical difficulty is great, the yield is low, and the cost is relatively high.
Chinese patent CN201310298423.1 discloses an iron sucrose injection and a preparation method thereof, wherein the product adopts the processes of activated carbon adsorption and damp-heat sterilization, the detection rate of visible foreign matters is reduced, but the influence of sterilization on ferrous iron impurities is not mentioned, the pH is required to be frequently regulated by using the activated carbon adsorption process, the operation is complex, serious three wastes are brought, and the amplified production is difficult.
Chinese patent CN201610621284.5 discloses an iron sucrose injection and a preparation method thereof, and the product prescription comprises iron sucrose, a stabilizer, a bacteriostatic agent, an acid-base regulator and water for injection. The prescription improves the stability of the product, can be sterilized by an overkill method, and improves the sterility assurance level. However, for the imitation of injection, the prescription is generally required to be consistent with the original research, and the stabilizer and the bacteriostat are added to the product, so that the medication risk is increased. The patent also does not mention the effect of sterilization on ferrous impurities.
Disclosure of Invention
The invention aims to overcome the defect that ferrous impurities are obviously increased in the wet heat sterilization process of an iron sucrose injection, and provides an iron sucrose composition, a preparation method and application thereof. The composition provided by the invention can be used for preparing the iron sucrose injection, and the process has few impurities and wide application prospect.
The invention provides an iron sucrose composition, which comprises iron sucrose, a stabilizer and water;
the stabilizer is selected from 1, 2 or 3 of dissolved oxygen, ozone and hydrogen peroxide.
It will be understood by those skilled in the art that the dissolved oxygen refers to the oxygen contained in the iron sucrose composition by supplementation (additional addition) to the iron sucrose composition, rather than the oxygen contained in the iron sucrose composition under natural conditions (conventional in the art).
In one embodiment, the iron sucrose composition further comprises a pH adjustor.
In one embodiment, the pH adjustor is conventional in the art, such as sodium hydroxide.
In one embodiment, the water is water for injection.
In one embodiment, the stabilizer may be dissolved oxygen, ozone or hydrogen peroxide, preferably dissolved oxygen or hydrogen peroxide, and more preferably hydrogen peroxide.
In one embodiment, the iron sucrose composition has a pH that is conventional in the art, preferably from 10.5 to 11.1. The pH may be obtained by adding a pH adjustor as described above.
In one embodiment, the iron sucrose composition has an iron sucrose content that is conventional in the art, preferably the iron sucrose content is from 10g/L to 30g/L, e.g., 20g/L, 25g/L, or 12.5g/L, as iron, with g/L being the ratio of the mass of the components to the volume of the iron sucrose composition.
In one scheme, in the iron sucrose composition, the dissolved oxygen content is 10 mg/L-21 mg/L; for example, 13mg/L, 11.6mg/L or 20.5mg/L, preferably 15mg/L to 21mg/L, the mg/L being the ratio of the mass of the components to the volume of the iron sucrose composition.
In a certain scheme, in the iron sucrose composition, the ozone content is 3 mg/L-10 mg/L; for example 4.5mg/L, 3.3mg/L or 6.2mg/L, preferably 3mg/L to 7mg/L, mg/L being the ratio of the mass of the components to the volume of the iron sucrose composition.
In one embodiment, the hydrogen peroxide content in the iron sucrose composition is 0.1g/L to 6g/L%, for example 0.5g/L to 5g/L, preferably 1g/L, 0.5g/L, 5g/L or 3g/L, where g/L is the ratio of the component mass to the iron sucrose composition volume.
In one embodiment, the iron sucrose composition has a ferrous iron content of 0.01% to 0.38%, for example 0.1% or 0.2%, and% is the ratio of ferrous iron mass to iron sucrose mass.
In one embodiment, the stabilizer is heated to sterilize and then all the stabilizer is decomposed, for example, the ozone is all decomposed into oxygen and the hydrogen peroxide is all decomposed into oxygen and water.
In one embodiment, when the stabilizer comprises hydrogen peroxide, the hydrogen peroxide may be used with a portion of the water in the form of hydrogen peroxide.
In one aspect, the iron sucrose composition is composed of iron sucrose, a stabilizer, a pH adjustor and water, wherein the kinds and contents of the iron sucrose, the stabilizer, the pH adjustor and the water are as described in any one of the present inventions.
In one embodiment, the iron sucrose composition is any one of the following:
iron sucrose composition 1: consists of 11.6mg/L dissolved oxygen, 20g/L iron sucrose, a pH regulator and water, wherein the sum of the contents of the dissolved oxygen, the iron sucrose, the pH regulator and the water is 100 percent;
Iron sucrose composition 2: consists of 20.5mg/L dissolved oxygen, 20g/L iron sucrose, a pH regulator and water, wherein the sum of the contents of the dissolved oxygen, the iron sucrose, the pH regulator and the water is 100 percent;
iron sucrose composition 3: consists of 3.3mg/L ozone, 20g/L iron sucrose, a pH regulator and water, wherein the sum of the contents of the ozone, the iron sucrose, the pH regulator and the water is 100 percent;
iron sucrose composition 4: consists of 6.2mg/L ozone, 20g/L iron sucrose, a pH regulator and water, wherein the sum of the contents of the ozone, the iron sucrose, the pH regulator and the water is 100 percent;
Iron sucrose composition 5: consists of 0.5g/L hydrogen peroxide, 20g/L iron sucrose, a pH regulator and water, wherein the sum of the contents of the hydrogen peroxide, the iron sucrose, the pH regulator and the water is 100 percent;
iron sucrose composition 6: consists of 5g/L hydrogen peroxide, 20g/L iron sucrose, a pH regulator and water, wherein the sum of the contents of the hydrogen peroxide, the iron sucrose, the pH regulator and the water is 100 percent;
iron sucrose composition 7: consists of 3g/L hydrogen peroxide, 25g/L iron sucrose, a pH regulator and water, wherein the sum of the contents of the hydrogen peroxide, the iron sucrose, the pH regulator and the water is 100 percent;
Iron sucrose composition 8: consists of 3g/L hydrogen peroxide, 12.5g/L iron sucrose, a pH regulator and water, wherein the sum of the contents of the hydrogen peroxide, the iron sucrose, the pH regulator and the water is 100 percent;
wherein mg/L and g/L are the ratio of the mass of the components to the volume of the iron sucrose composition, and the iron sucrose content is the content calculated by iron.
The invention provides a preparation method of an iron sucrose composition, which comprises the following steps:
mixing iron sucrose, a stabilizer and water to obtain an iron sucrose composition;
Wherein the kinds and contents of the water, the iron sucrose and the stabilizer are as described in any one of the present invention.
In one embodiment, the preparation method comprises the steps of:
And mixing the sucrose molten iron solution containing the sucrose iron and part of water with a stabilizer and the rest water to obtain the sucrose iron composition.
In the preparation method, the pH of the sucrose molten iron solution is conventional in the art, for example, 10.5 to 11.1. The pH may be obtained by adding a pH adjustor as described above.
In the preparation method, the mass ratio of part of water in the sucrose molten iron solution to water in the sucrose molten iron composition can be 65% -85%, preferably 65%, 70%, 75% or 85%.
In the preparation method, when the stabilizer contains hydrogen peroxide, the hydrogen peroxide is conventional in the art, for example, 0.1% -30% hydrogen peroxide, preferably 0.2% -10% hydrogen peroxide, and for example, 0.5%, 5% or 3% hydrogen peroxide; % refers to the mass fraction of hydrogen peroxide to hydrogen peroxide.
In the preparation method, when the stabilizer is dissolved oxygen and/or ozone, the preparation method can comprise the following steps: and mixing the sucrose molten iron solution and the rest water to obtain a mixture B, and introducing one or more of air, oxygen and ozone into the mixture B.
In the preparation method, when the stabilizer is hydrogen peroxide, the method comprises the following steps: and mixing the sucrose molten iron solution with hydrogen peroxide to obtain a mixture A, and mixing the mixture A with the rest water.
In one embodiment, the preparation method may further comprise the steps of:
mixing part of water with the sucrose iron to obtain the sucrose molten iron solution, and adjusting the pH value of the sucrose molten iron solution.
In the preparation method, the part of water can be 65% -85%, such as 65%, 70%, 75% or 85%, of the total amount of water in the iron sucrose composition, and the% is the mass percentage of the part of water and the water in the iron sucrose composition.
In the preparation method, in the mixing of a part of water with iron sucrose, the mixing temperature is conventional in the art, for example, 5 to 40 ℃, preferably 5 to 35 ℃, further preferably 5 to 20 ℃, 12 to 20 ℃ or 12 to 35 ℃.
In the preparation method, the temperature of the solution at the time of the adjustment (adjustment of the pH of the sucrose molten iron solution) is conventional in the art, for example, 5 to 25 ℃, preferably 5 to 20 ℃, 12 to 20 ℃, or 12 to 25 ℃.
In the preparation method, the pH is adjusted (pH of the sucrose molten iron solution is adjusted) as usual in the art, for example, pH is adjusted using NaOH, preferably 0.5 to 2mol/L NaOH solution (for example, 1mol/L NaOH solution) is used.
In the preparation method, the adjusting (adjusting the pH of the sucrose molten iron solution) of the pH may be adjusting the pH to 10.5 to 11.1.
In the preparation method, in the step of mixing part of water with the iron sucrose, the mixing can be mixed and dissolved.
In one embodiment, the preparation method may further comprise the following post-treatment steps:
Filtering, canning and sealing the iron sucrose composition.
In the preparation method, in the post-treatment step, the filtration is conventional in the art, preferably twice, wherein the first filtration adopts a circulating filtration mode, the pore diameter of the filter is 0.22-0.45 μm (for example, 0.22 μm and/or 0.45 μm), and the second filtration adopts a filter with the pore diameter of 0.22 μm.
In the preparation method, the time for the cyclic filtration may be more than 30 minutes, for example, 31 minutes.
In the preparation method, in the post-treatment step, the filling is conventional in the art, for example, the filling is carried out in 5mL ampoules, and preferably, the iron sucrose content in each ampoule is 100mg in terms of iron.
In the preparation method, in the post-treatment step, the canned container can be subjected to solvent sealing, preferably before the solvent sealing, and air or oxygen is further introduced into the container.
It will be appreciated by those skilled in the art that to maintain process suitability, the further gas feed into the filling vessel prior to the melt sealing should be the same as the gas feed into the molten sucrose iron solution and the water mixture (mixture B above), for example both air or oxygen.
In one embodiment, the method for preparing the iron sucrose composition comprises the steps of:
mixing sucrose iron and part of water accounting for 65-85% of the total water mass ratio in the sucrose iron composition at 5-40 ℃ to obtain sucrose molten iron solution, and adjusting (for example, adjusting by using NaOH) the pH value of the sucrose molten iron solution to 10.5-11.1 at 5-25 ℃;
Mixing the sucrose molten iron solution with water, and introducing one or more of air, oxygen and ozone to obtain the sucrose molten iron composition; or mixing the sucrose molten iron solution with hydrogen peroxide, and adding the rest water to obtain the sucrose molten iron composition;
Filtering the iron sucrose composition twice, filling and sealing;
Wherein, the twice filtration conditions are: first filtering: a two-stage filter with pore diameters of 0.45 μm and/or 0.22 μm for more than 30 minutes (for example, 31 minutes); and (3) secondary filtration: the filter with pore size of 0.22 μm was used for filtration.
The invention provides an application of the iron sucrose composition in preparing an iron sucrose injection.
In one scheme, the application of the iron sucrose composition in preparing the iron sucrose injection comprises the following steps of sterilizing the iron sucrose composition to obtain the iron sucrose injection.
In such applications, the sterilization is conventional in the art, and it is preferable to use the overkill method (F0. Gtoreq.12) for moist heat sterilization, for example, treatment at 121℃for 12 minutes.
The application preferably comprises the following post-treatment steps: and after sterilization, performing leak detection, lamp inspection and packaging procedures to obtain the iron sucrose injection.
In one embodiment, the application of the iron sucrose composition in preparing the iron sucrose injection further comprises the following steps: the iron sucrose composition was prepared as described above for the preparation of the iron sucrose composition.
The above preferred conditions can be arbitrarily combined on the basis of not deviating from the common knowledge in the art, and thus, each preferred embodiment of the present invention can be obtained.
The reagents and materials used in the present invention are commercially available.
The invention has the positive progress effects that: the iron sucrose composition provided by the invention can be used for producing iron sucrose injection, the content of ferrous impurities in the iron sucrose injection in the production process can be effectively controlled, the added stabilizer does not influence the prescription composition of the product, the operation is simple and convenient, and the industrialized operation is convenient.
Detailed Description
The invention is further illustrated by means of the following examples, which are not intended to limit the scope of the invention. The experimental methods, in which specific conditions are not noted in the following examples, were selected according to conventional methods and conditions, or according to the commercial specifications.
Raw materials and testing method:
iron sucrose: purchasing from Anhui cloud sail pharmaceutical Co.Ltd
Dissolved oxygen: and (3) measuring by adopting a Metreler multiple parameter tester at room temperature.
Ozone: the liquid to be measured was diluted 50 times with purified water and then measured by chemical analysis (iodine method).
The ferrous iron measuring method comprises the following steps: measuring by using a voltammetry, taking 12ml of sodium acetate buffer solution (pH 7.0) into a polarographic pool, immersing an electrode into the solution, charging nitrogen for 300 seconds, taking 40ul of injection, charging nitrogen for 30 seconds to fully mix, measuring, simultaneously performing a blank test, deducting the blank, and calculating to obtain the electrode.
Example 1
The prescription is shown in table 1:
TABLE 1
| Raw and auxiliary materials | Dosage of |
| Iron sucrose (iron) | 20g |
| Sodium hydroxide solution (2M) | Regulating pH to 10.5-11.1 |
| Water for injection | To 1000ml |
| Air-conditioner | Proper amount of |
S1: adding 85% of water for injection into a liquid preparation tank, controlling the water temperature to be 5-20 ℃, starting stirring, adding the iron sucrose raw material medicine, and stirring until the solution is clear;
s2: controlling the water temperature to be 5-20 ℃; adjusting pH to 10.5-11.1 with sodium hydroxide solution (pH adjusting solution);
S3: adding water for injection to the full amount, and then introducing air into the solution, wherein the air is stirred in the air introducing process until the oxygen content in the injection is 11.6mg/L;
S4: the liquid medicine is circularly filtered by a secondary filter (aperture: 0.45 μm, 0.22 μm) for more than 30 minutes; description: the two-stage filter has 2 filters with the pore sizes as above.
S5: the liquid medicine was filtered through a primary filter (pore diameter: 0.22 μm), and then filled into 5ml glass ampoules (specification: each containing iron sucrose, calculated as iron, 100 mg), and sealed.
S6: and (3) transferring the filled product into a sterilizing cabinet, and carrying out damp-heat sterilization at 121 ℃/12 minutes.
S7: the product is subjected to the procedures of leak detection, lamp inspection and packaging to obtain the iron sucrose injection.
Example 2
The prescription is shown in Table 2:
TABLE 2
| Raw and auxiliary materials | Dosage of |
| Iron sucrose (iron) | 20g |
| Sodium hydroxide solution (1M) | Regulating pH to 10.5-11.1 |
| Water for injection | To 1000ml |
| Oxygen gas | Proper amount of |
S1: adding 75% of injection water into a liquid preparation tank, controlling the water temperature to be 12-20 ℃, starting stirring, adding the iron sucrose raw material medicine, and stirring until the solution is clear;
S2: controlling the water temperature to be 12-20 ℃; adjusting pH to 10.5-11.1 with sodium hydroxide solution (pH adjusting solution);
s3: adding water for injection to the full amount, and then introducing oxygen into the solution, wherein the aeration process is kept stirring until the oxygen content in the injection is 20.5mg/L;
S4: the liquid medicine is circularly filtered by a secondary filter (aperture: 0.45 μm, 0.22 μm) for more than 30 minutes;
S5: filtering the liquid medicine by a primary filter (aperture: 0.22 μm), filling into 5ml glass ampoule (specification: each containing iron sucrose is 100mg in terms of iron), introducing appropriate amount of oxygen into the upper part of ampoule bottle, and sealing.
S6: and (3) transferring the filled product into a sterilizing cabinet, and carrying out damp-heat sterilization at 121 ℃/12 minutes.
S7: the product is subjected to the procedures of leak detection, lamp inspection and packaging to obtain the iron sucrose injection.
Example 3
The prescription is shown in Table 3:
TABLE 3 Table 3
| Raw and auxiliary materials | Dosage of |
| Iron sucrose (iron) | 20g |
| Sodium hydroxide solution (0.5M) | Regulating pH to 10.5-11.1 |
| Water for injection | To 1000ml |
| Ozone (decomposition after damp heat sterilization) | Proper amount of |
S1: adding 65% of injection water into a liquid preparation tank, controlling the water temperature to be 12-35 ℃, starting stirring, adding the iron sucrose raw material medicine, and stirring until the solution is clear;
s2: controlling the water temperature to be 12-25 ℃; adjusting pH to 10.5-11.1 with sodium hydroxide solution (pH adjusting solution);
s3: adding water for injection to the full amount, and then introducing ozone into the solution, wherein the ozone is kept stirring in the aeration process until the ozone content in the injection is 3.3mg/L;
S4: the liquid medicine is circularly filtered by a secondary filter (aperture: 0.45 μm, 0.22 μm) for more than 30 minutes;
s5: the liquid medicine was filtered through a primary filter (pore diameter: 0.22 μm), and then filled into 5ml glass ampoules (specification: each containing iron sucrose, calculated as iron, 100 mg), and sealed.
S6: and (3) transferring the filled product into a sterilizing cabinet, and carrying out damp-heat sterilization at 121 ℃/12 minutes.
S7: the product is subjected to the procedures of leak detection, lamp inspection and packaging to obtain the iron sucrose injection.
Example 4
The prescription is shown in Table 4:
TABLE 4 Table 4
| Raw and auxiliary materials | Dosage of |
| Iron sucrose (iron) | 20g |
| Sodium hydroxide solution (1M) | Regulating pH to 10.5-11.1 |
| Water for injection | To 1000ml |
| Ozone (decomposition after damp heat sterilization) | Proper amount of |
S1: adding 75% of injection water into a liquid preparation tank, controlling the water temperature to be 12-35 ℃, starting stirring, adding the iron sucrose raw material medicine, and stirring until the solution is clear;
s2: controlling the water temperature to be 12-25 ℃; adjusting pH to 10.5-11.1 with sodium hydroxide solution (pH adjusting solution);
s3: adding water for injection to the full amount, and then introducing ozone into the solution, wherein the ozone is maintained to be stirred in the aeration process until the ozone content in the injection is 6.2mg/L;
S4: the liquid medicine is circularly filtered by a secondary filter (aperture: 0.45 μm, 0.22 μm) for more than 30 minutes;
s5: the liquid medicine was filtered through a primary filter (pore diameter: 0.22 μm), and then filled into 5ml glass ampoules (specification: each containing iron sucrose, calculated as iron, 100 mg), and sealed.
S6: and (3) transferring the filled product into a sterilizing cabinet, and carrying out damp-heat sterilization at 121 ℃/12 minutes.
S7: the product is subjected to the procedures of leak detection, lamp inspection and packaging to obtain the iron sucrose injection.
Example 5
The prescription is shown in Table 5:
TABLE 5
S1: adding 70% of injection water into a liquid preparation tank, controlling the water temperature to be 12-35 ℃, starting stirring, adding the iron sucrose raw material medicine, and stirring until the solution is clear;
s2: controlling the water temperature to be 12-25 ℃; adjusting pH to 10.5-11.1 with sodium hydroxide solution (pH adjusting solution);
s3: adding 0.5% of hydrogen peroxide with the prescription amount into the solution, uniformly stirring, and adding water for injection to the full amount (injection: the concentration of hydrogen peroxide in the injection is 0.5 g/L);
S4: the liquid medicine is circularly filtered by a secondary filter (aperture: 0.45 μm, 0.22 μm) for more than 30 minutes;
s5: the liquid medicine was filtered through a primary filter (pore diameter: 0.22 μm), and then filled into 5ml glass ampoules (specification: each containing iron sucrose, calculated as iron, 100 mg), and sealed.
S6: and (3) transferring the filled product into a sterilizing cabinet, and carrying out damp-heat sterilization at 121 ℃/12 minutes.
S7: the product is subjected to the procedures of leak detection, lamp inspection and packaging to obtain the iron sucrose injection.
Example 6
The prescription is shown in Table 6:
TABLE 6
| Raw and auxiliary materials | Dosage of |
| Iron sucrose (iron) | 20g |
| Sodium hydroxide solution (1M) | Regulating pH to 10.5-11.1 |
| 5% Hydrogen peroxide (decomposition after wet heat sterilization) | 100ml |
| Water for injection | To 1000ml |
S1: adding 70% of injection water into a liquid preparation tank, controlling the water temperature to be 12-35 ℃, starting stirring, adding the iron sucrose raw material medicine, and stirring until the solution is clear;
s2: controlling the water temperature to be 12-25 ℃; adjusting pH to 10.5-11.1 with sodium hydroxide solution (pH adjusting solution);
S3: adding 5% of hydrogen peroxide with the prescription amount into the solution, uniformly stirring, and then adding water for injection to the full amount (injection: the concentration of the hydrogen peroxide in the injection is 5 g/L);
S4: the liquid medicine is circularly filtered by a secondary filter (aperture: 0.45 μm, 0.22 μm) for more than 30 minutes;
s5: the liquid medicine was filtered through a primary filter (pore diameter: 0.22 μm), and then filled into 5ml glass ampoules (specification: each containing iron sucrose, calculated as iron, 100 mg), and sealed.
S6: and (3) transferring the filled product into a sterilizing cabinet, and carrying out damp-heat sterilization at 121 ℃/12 minutes.
S7: the product is subjected to the procedures of leak detection, lamp inspection and packaging to obtain the iron sucrose injection.
Example 7
The prescription is shown in Table 7:
TABLE 7
| Raw and auxiliary materials | Dosage of |
| Iron sucrose (iron) | 25g |
| Sodium hydroxide solution (1M) | Regulating pH to 10.5-11.1 |
| 3% Hydrogen peroxide (decomposition after wet heat sterilization) | 100ml |
| Water for injection | To 1000ml |
S1: adding 70% of injection water into a liquid preparation tank, controlling the water temperature to be 12-35 ℃, starting stirring, adding the iron sucrose raw material medicine, and stirring until the solution is clear;
s2: controlling the water temperature to be 12-25 ℃; adjusting pH to 10.5-11.1 with sodium hydroxide solution (pH adjusting solution);
S3: adding 3% of hydrogen peroxide with the prescription amount into the solution, uniformly stirring, and then adding water for injection to the full amount (injection: the concentration of the hydrogen peroxide in the injection is 3 g/L);
S4: the liquid medicine is circularly filtered by a secondary filter (aperture: 0.45 μm, 0.22 μm) for more than 30 minutes;
s5: the liquid medicine was filtered through a primary filter (pore diameter: 0.22 μm), and then filled into 5ml glass ampoules (specification: each containing iron sucrose, calculated as iron, 100 mg), and sealed.
S6: and (3) transferring the filled product into a sterilizing cabinet, and carrying out damp-heat sterilization at 121 ℃/12 minutes.
S7: the product is subjected to the procedures of leak detection, lamp inspection and packaging to obtain the iron sucrose injection.
Example 8
The prescription is shown in Table 8:
TABLE 8
S1: adding 70% of injection water into a liquid preparation tank, controlling the water temperature to be 12-35 ℃, starting stirring, adding the iron sucrose raw material medicine, and stirring until the solution is clear;
s2: controlling the water temperature to be 12-25 ℃; adjusting pH to 10.5-11.1 with sodium hydroxide solution (pH adjusting solution);
S3: adding 3% of hydrogen peroxide with the prescription amount into the solution, uniformly stirring, and then adding water for injection to the full amount (injection: the concentration of the hydrogen peroxide in the injection is 3 g/L);
S4: the liquid medicine is circularly filtered by a secondary filter (aperture: 0.45 μm, 0.22 μm) for more than 30 minutes;
S5: the liquid medicine was filtered through a primary filter (pore diameter: 0.22 μm), filled into 10ml glass ampoules (specification: each containing iron sucrose, calculated as iron, 100 mg), and sealed.
S6: and (3) transferring the filled product into a sterilizing cabinet, and carrying out damp-heat sterilization at 121 ℃/12 minutes.
S7: the product is subjected to the procedures of leak detection, lamp inspection and packaging to obtain the iron sucrose injection.
Comparative example 1
The prescription is shown in Table 9:
TABLE 9
| Raw and auxiliary materials | Dosage of |
| Iron sucrose (iron) | 20g |
| Sodium hydroxide solution (1M) | Regulating pH to 10.5-11.1 |
| Water for injection | To 1000ml |
S1: adding 80% of injection water into a liquid preparation tank, controlling the water temperature to be 5-20 ℃, starting stirring, adding the iron sucrose raw material medicine, and stirring until the solution is clear;
s2: controlling the water temperature to be 5-20 ℃; adjusting pH to 10.5-11.1 with sodium hydroxide solution (pH adjusting solution);
S3: adding water for injection to the full amount;
S4: the liquid medicine is circularly filtered by a secondary filter (aperture: 0.45 μm, 0.22 μm) for more than 30 minutes;
s5: the liquid medicine was filtered through a primary filter (pore diameter: 0.22 μm), and then filled into 5ml glass ampoules (specification: each containing iron sucrose, calculated as iron, 100 mg), and sealed.
S6: and (3) transferring the filled product into a sterilizing cabinet, and carrying out damp-heat sterilization at 121 ℃/12 minutes.
S7: the product is subjected to the procedures of leak detection, lamp inspection and packaging to obtain the iron sucrose injection.
Comparative example 2
The prescription is shown in Table 10:
Table 10
S1: adding 70% of injection water into a liquid preparation tank, controlling the water temperature to be 12-35 ℃, starting stirring, adding the iron sucrose raw material medicine, and stirring until the solution is clear;
s2: controlling the water temperature to be 12-25 ℃; adjusting pH to 10.5-11.1 with sodium hydroxide solution (pH adjusting solution);
s3: adding 10% of hydrogen peroxide with the prescription amount into the solution, uniformly stirring, and then adding water for injection to the full amount (injection: the concentration of hydrogen peroxide in the injection is 10 g/L);
S4: the liquid medicine is circularly filtered by a secondary filter (aperture: 0.45 μm, 0.22 μm) for more than 30 minutes;
s5: the liquid medicine was filtered through a primary filter (pore diameter: 0.22 μm), and then filled into 5ml glass ampoules (specification: each containing iron sucrose, calculated as iron, 100 mg), and sealed.
S6: and (3) transferring the filled product into a sterilizing cabinet, and carrying out damp-heat sterilization at 121 ℃/12 minutes.
S7: the product is subjected to the procedures of leak detection, lamp inspection and packaging to obtain the iron sucrose injection.
Comparative example 3
The prescription is shown in Table 11:
TABLE 11
| Raw and auxiliary materials | Dosage of |
| Iron sucrose (iron) | 20g |
| Sodium hydroxide solution (1M) | Regulating pH to 10.5-11.1 |
| Water for injection | To 1000ml |
| Ozone (decomposition after damp heat sterilization) | Proper amount of |
S1: adding 75% of injection water into a liquid preparation tank, controlling the water temperature to be 12-35 ℃, starting stirring, adding the iron sucrose raw material medicine, and stirring until the solution is clear;
s2: controlling the water temperature to be 12-25 ℃; adjusting pH to 10.5-11.1 with sodium hydroxide solution (pH adjusting solution);
s3: adding water for injection to the full amount, and then introducing ozone into the solution, wherein the ozone is maintained to be stirred in the aeration process until the ozone content in the injection is 11.6mg/L;
s4: the liquid medicine is circularly filtered by a secondary filter (aperture: 0.45 μm or 0.22 μm) for more than 30 minutes;
s5: the liquid medicine was filtered through a primary filter (pore diameter: 0.22 μm), and then filled into 5ml glass ampoules (specification: each containing iron sucrose, calculated as iron, 100 mg), and sealed.
S6: and (3) transferring the filled product into a sterilizing cabinet, and carrying out damp-heat sterilization at 121 ℃/12 minutes.
S7: the product is subjected to the procedures of leak detection, lamp inspection and packaging to obtain the iron sucrose injection.
Effect example 1
Comparative examples 1, 2,3, 4, 5, 6,7 and 1, 2 and 3 show the changes in ferrous iron and sucrose content before and after wet heat sterilization and ampoule breakage after sterilization, and the results are shown in tables 12 and 13.
Table 12
The results show that examples 1 to 8 significantly reduced the increase in ferrous iron after the addition of the stabilizer under the same sterilization conditions relative to comparative example 1.
TABLE 13
The results show that the concentration of hydrogen peroxide and ozone is too high, the sucrose content is slightly reduced after sterilization, the concentration of hydrogen peroxide is too high, and the ampoule bottle is easy to break after sterilization.
The sucrose content determination method in the iron sucrose injection adopts high performance liquid chromatography (differential detector).
Claims (10)
1. An iron sucrose composition, characterized in that it is prepared by the following method:
the prescription is shown in the following table:
S1: adding 85% of water for injection into a liquid preparation tank, controlling the water temperature to be 5-20 ℃, starting stirring, adding the iron sucrose raw material medicine, and stirring until the solution is clear;
S2: controlling the water temperature to be 5-20 ℃; adjusting pH to 10.5-11.1 with sodium hydroxide solution;
s3: adding water for injection to the full amount, and then introducing air into the solution, wherein the air is stirred in the air introducing process until the oxygen content in the injection is 11.6 mg/L;
S4: the liquid medicine is filtered by a secondary filter for more than 30 minutes in a circulating way; two-stage filter, there are 2 filters, aperture: 0.45 μm, 0.22 μm;
S5: the liquid medicine passes through a primary filter with the aperture: after filtration, 0.22 μm was filled into 5ml glass ampoules, each containing 100mg of iron sucrose as iron, and sealed.
2. An iron sucrose composition, characterized in that it is prepared by the following method:
The prescription is shown in the following table:
S1: adding 70% of injection water into a liquid preparation tank, controlling the water temperature to be 12-35 ℃, starting stirring, adding the iron sucrose raw material medicine, and stirring until the solution is clear;
S2: controlling the water temperature to be 12-25 ℃; adjusting pH to 10.5-11.1 with sodium hydroxide solution;
S3: adding 0.5% of hydrogen peroxide with the prescription amount into the solution, uniformly stirring, and adding water for injection to the full amount, wherein the concentration of the hydrogen peroxide in the injection is 0.5g/L;
S4: the liquid medicine passes through a secondary filter with the aperture: circularly filtering for more than 30 minutes at 0.45 mu m and 0.22 mu m;
S5: the liquid medicine passes through a primary filter with the aperture: after filtration, 0.22 μm was filled into 5ml glass ampoules, each containing 100mg of iron sucrose as iron, and sealed.
3. An iron sucrose composition, characterized in that it is prepared by the following method:
The prescription is shown in the following table:
S1: adding 70% of injection water into a liquid preparation tank, controlling the water temperature to be 12-35 ℃, starting stirring, adding the iron sucrose raw material medicine, and stirring until the solution is clear;
S2: controlling the water temperature to be 12-25 ℃; adjusting pH to 10.5-11.1 with sodium hydroxide solution;
S3: adding 5% of hydrogen peroxide with the prescription amount into the solution, uniformly stirring, and then adding water for injection to the full amount, wherein the concentration of the hydrogen peroxide in the injection is 5g/L;
S4: the liquid medicine passes through a secondary filter with the aperture: circularly filtering for more than 30 minutes at 0.45 mu m and 0.22 mu m;
S5: the liquid medicine passes through a primary filter with the aperture: after filtration, 0.22 μm was filled into 5ml glass ampoules, each containing 100mg of iron sucrose as iron, and sealed.
4. An iron sucrose composition, characterized in that it is prepared by the following method:
The prescription is shown in the following table:
S1: adding 70% of injection water into a liquid preparation tank, controlling the water temperature to be 12-35 ℃, starting stirring, adding the iron sucrose raw material medicine, and stirring until the solution is clear;
S2: controlling the water temperature to be 12-25 ℃; adjusting pH to 10.5-11.1 with sodium hydroxide solution;
s3: adding 3% of hydrogen peroxide with the prescription amount into the solution, uniformly stirring, and then adding water for injection to the full amount, wherein the concentration of the hydrogen peroxide in the injection is 3g/L;
S4: the liquid medicine passes through a secondary filter with the aperture: circularly filtering for more than 30 minutes at 0.45 mu m and 0.22 mu m;
S5: the liquid medicine passes through a primary filter with the aperture: after filtration, 0.22 μm was filled into 5ml glass ampoules, each containing 100mg of iron sucrose as iron, and sealed.
5. An iron sucrose composition, characterized in that it is prepared by the following method:
The prescription is shown in the following table:
S1: adding 70% of injection water into a liquid preparation tank, controlling the water temperature to be 12-35 ℃, starting stirring, adding the iron sucrose raw material medicine, and stirring until the solution is clear;
S2: controlling the water temperature to be 12-25 ℃; adjusting pH to 10.5-11.1 with sodium hydroxide solution;
s3: adding 3% of hydrogen peroxide with the prescription amount into the solution, uniformly stirring, and then adding water for injection to the full amount, wherein the concentration of the hydrogen peroxide in the injection is 3g/L;
S4: the liquid medicine passes through a secondary filter with the aperture: circularly filtering for more than 30 minutes at 0.45 mu m and 0.22 mu m;
S5: the liquid medicine passes through a primary filter with the aperture: after filtration, 0.22 μm was filled into 10ml glass ampoules, each containing 100mg of iron sucrose as iron, and sealed.
6. Use of the iron sucrose composition according to any one of claims 1-5 in the preparation of an iron sucrose injection.
7. Use of the iron sucrose composition according to claim 6 for the preparation of an iron sucrose injection, wherein the use comprises the steps of:
sterilizing the iron sucrose composition to obtain the iron sucrose injection.
8. The use of the iron sucrose composition as set forth in claim 7 for preparing an iron sucrose injection,
In the application, the sterilization is wet heat sterilization by adopting an over-sterilization method.
9. Use of the iron sucrose composition according to claim 7 for the preparation of an iron sucrose injection, wherein in the use the sterilization is performed at 121 ℃ for 12min.
10. The use of the iron sucrose composition as set forth in claim 7 for preparing an iron sucrose injection,
The application comprises the following post-processing steps: and after sterilization, performing leak detection, lamp inspection and packaging procedures to obtain the iron sucrose injection.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103622979A (en) * | 2012-08-21 | 2014-03-12 | 天津中敖生物科技有限公司 | Preparation method of iron sucrose bulk drug and injection |
| CN106137953A (en) * | 2016-08-01 | 2016-11-23 | 嘉实（湖南）医药科技有限公司 | Iron sucrose injection and preparation method thereof |
| CN115177625A (en) * | 2022-06-28 | 2022-10-14 | 金陵药业股份有限公司 | Carboxyl ferric maltose pharmaceutical composition and preparation method thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103622979A (en) * | 2012-08-21 | 2014-03-12 | 天津中敖生物科技有限公司 | Preparation method of iron sucrose bulk drug and injection |
| CN106137953A (en) * | 2016-08-01 | 2016-11-23 | 嘉实（湖南）医药科技有限公司 | Iron sucrose injection and preparation method thereof |
| CN115177625A (en) * | 2022-06-28 | 2022-10-14 | 金陵药业股份有限公司 | Carboxyl ferric maltose pharmaceutical composition and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 蔗糖铁注射液铁含量测定方法的研究;李莉等;药学与临床研究;第19卷(第5期);414-416 * |
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