CN113413927A - Method for removing antioxidant sulfite in compound amino acid injection - Google Patents
Method for removing antioxidant sulfite in compound amino acid injection Download PDFInfo
- Publication number
- CN113413927A CN113413927A CN202110678096.7A CN202110678096A CN113413927A CN 113413927 A CN113413927 A CN 113413927A CN 202110678096 A CN202110678096 A CN 202110678096A CN 113413927 A CN113413927 A CN 113413927A
- Authority
- CN
- China
- Prior art keywords
- sulfite
- amino acid
- compound amino
- antioxidant
- acid injection
- 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.)
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Links
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 238000002347 injection Methods 0.000 title claims abstract description 34
- 239000007924 injection Substances 0.000 title claims abstract description 34
- -1 compound amino acid Chemical class 0.000 title claims abstract description 26
- 238000000034 method Methods 0.000 title claims abstract description 24
- 239000003963 antioxidant agent Substances 0.000 title claims abstract description 22
- 230000003078 antioxidant effect Effects 0.000 title claims abstract description 22
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003456 ion exchange resin Substances 0.000 claims abstract description 7
- 229920003303 ion-exchange polymer Polymers 0.000 claims abstract description 7
- FSJWWSXPIWGYKC-UHFFFAOYSA-M silver;silver;sulfanide Chemical compound [SH-].[Ag].[Ag+] FSJWWSXPIWGYKC-UHFFFAOYSA-M 0.000 claims abstract description 6
- 229910052946 acanthite Inorganic materials 0.000 claims abstract description 5
- XUARKZBEFFVFRG-UHFFFAOYSA-N silver sulfide Chemical compound [S-2].[Ag+].[Ag+] XUARKZBEFFVFRG-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229940056910 silver sulfide Drugs 0.000 claims abstract description 5
- 239000003463 adsorbent Substances 0.000 claims abstract description 3
- 229920000642 polymer Polymers 0.000 claims description 8
- 239000003729 cation exchange resin Substances 0.000 claims description 6
- 239000002131 composite material Substances 0.000 claims description 6
- 229920001577 copolymer Polymers 0.000 claims description 6
- 239000004005 microsphere Substances 0.000 claims description 6
- YPEMKASELPCGPB-UHFFFAOYSA-N 2-methylprop-2-enoic acid;prop-2-enamide Chemical compound NC(=O)C=C.CC(=C)C(O)=O YPEMKASELPCGPB-UHFFFAOYSA-N 0.000 claims description 4
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical group C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 4
- 229920003145 methacrylic acid copolymer Polymers 0.000 claims description 4
- 229940117841 methacrylic acid copolymer Drugs 0.000 claims description 4
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 claims description 3
- 239000011347 resin Substances 0.000 claims description 3
- 229920005989 resin Polymers 0.000 claims description 3
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 2
- 229920000936 Agarose Chemical group 0.000 claims description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Chemical group 0.000 claims description 2
- 229920002678 cellulose Chemical group 0.000 claims description 2
- 239000001913 cellulose Chemical group 0.000 claims description 2
- 229920002451 polyvinyl alcohol Chemical group 0.000 claims description 2
- OCWNMDUAUUAHSJ-UHFFFAOYSA-N silver;sulfanylidenesilver Chemical compound [Ag].[Ag]=S OCWNMDUAUUAHSJ-UHFFFAOYSA-N 0.000 claims description 2
- 150000001413 amino acids Chemical class 0.000 abstract description 8
- 238000001179 sorption measurement Methods 0.000 abstract description 2
- 229940024606 amino acid Drugs 0.000 description 21
- 239000002245 particle Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 6
- 238000001802 infusion Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 229910052709 silver Inorganic materials 0.000 description 4
- 239000004332 silver Substances 0.000 description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 4
- 238000002791 soaking Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 235000010265 sodium sulphite Nutrition 0.000 description 3
- CHRJZRDFSQHIFI-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;styrene Chemical compound C=CC1=CC=CC=C1.C=CC1=CC=CC=C1C=C CHRJZRDFSQHIFI-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 229910001961 silver nitrate Inorganic materials 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- IFQSXNOEEPCSLW-DKWTVANSSA-N L-cysteine hydrochloride Chemical compound Cl.SC[C@H](N)C(O)=O IFQSXNOEEPCSLW-DKWTVANSSA-N 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 150000002734 metacrylic acid derivatives Chemical class 0.000 description 1
- 239000011806 microball Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J47/00—Ion-exchange processes in general; Apparatus therefor
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J47/00—Ion-exchange processes in general; Apparatus therefor
- B01J47/016—Modification or after-treatment of ion-exchangers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a method for removing antioxidant sulfite in compound amino acid injection, which comprises the following steps: the silver sulfide microspheres or the ion exchange resin loaded with silver sulfide are used as an adsorbent after being sterilized to adsorb and remove sulfite in the compound amino acid injection. The removal method provided by the invention can carry out specific adsorption on sulfite in the amino acid injection, so that the harm of sulfite to human bodies can be effectively eliminated while the storage stability of the injection is not reduced.
Description
Technical Field
The invention relates to the technical field of medical treatment, in particular to a method for removing antioxidant sulfite in compound amino acid injection.
Background
The compound amino acid injection is usually added with sulfite serving as an antioxidant to ensure the stability of amino acid, but the sulfite in the infusion has certain toxicity to organisms, because trace sulfite can prolong the prothrombin activation time, hinder the activity of urokinase fibrinolytic protein, cause allergy and the like, so the limit of sodium sulfite in the amino acid infusion recommended by the national drug administration is 0.1 percent.
At present, in order to reduce the content of sodium sulfite, the general solutions are mainly as follows: one is the addition of a mixed antioxidant such as 0.05% sulfite and 0.05% L-cysteine hydrochloride; and secondly, high-purity nitrogen is introduced into the tail end of the production to remove free oxygen in the solution so as to reduce the oxygen content causing the amino acid to be oxidized and discolored. In the method, the addition amount of the antioxidant sodium sulfite can be reduced only in a limited way, but the risk of oxidation loss of amino acid nutrients in the transportation and storage process is increased, and the problems of clinical allergy and the like caused by the fact that trace sulfite is input into a human body along with injection cannot be effectively solved.
Disclosure of Invention
Aiming at the problems, the method for removing the antioxidant sulfite in the compound amino acid injection is provided, aiming at effectively reducing the content of sulfite in the compound amino acid injection.
The specific technical scheme is as follows:
a method for removing the sulfite as the antioxidant in the compound amino acid injection features that the silver sulfide microballs or the ion exchange resin loaded with silver sulfide are sterilized and used as adsorbent to adsorb and remove the sulfite from the compound amino acid injection.
The method for removing the antioxidant sulfite in the compound amino acid injection also has the characteristic that the silver sulfide microspheres are one or more of hollow silver sulfide microspheres or silver sulfide-polymer gel composite microspheres.
The method for removing the antioxidant sulfite in the compound amino acid injection also has the characteristic that the polymer gel is acrylamide, methacrylic acid, acrylic acid, methacrylate and derivatives thereof or a copolymer of acrylate and derivatives thereof.
The method for removing the antioxidant sulfite in the compound amino acid injection also has the characteristic that the polymer gel is one of acrylamide-methacrylic acid copolymer, acrylamide-n-butyl methacrylate copolymer and acrylamide-methyl methacrylate copolymer.
The method for removing the antioxidant sulfite in the compound amino acid injection also has the characteristic that the ion exchange resin is porous cation exchange resin.
The method for removing the antioxidant sulfite of the compound amino acid injection also has the characteristic that the cation exchange resin is one of styrene, methacrylate series, cellulose series, agarose series or polyvinyl alcohol series exchange resin.
The beneficial effect of above-mentioned scheme is:
the removal method provided by the invention can carry out specific adsorption on sulfite in the amino acid injection, so that the harm of sulfite to human bodies can be effectively eliminated while the storage stability of the injection is not reduced.
Detailed Description
The technical solutions in the embodiments of the present invention will be described clearly and completely with reference to the following embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
It should be noted that the embodiments and features of the embodiments may be combined with each other without conflict.
The present invention is further illustrated by the following examples, which are not to be construed as limiting the invention.
Example 1
A method for removing antioxidant sulfite in compound amino acid injection comprises the following steps:
1) taking styrene-divinylbenzene macroporous cation exchange resin (Na type), putting the styrene-divinylbenzene macroporous cation exchange resin into a silver nitrate solution, slowly stirring for 6 hours, standing and soaking for 10 hours, taking out, washing with purified water until no free silver ions exist in washing liquid, and obtaining a cation exchange resin-silver ion precursor;
2) standing and soaking the precursor resin in a sodium thiosulfate solution for 1 hour, taking out after the reaction is finished, and washing with injection water until the number of particles with the particle size of 15-25 mu m is less than 200 and the number of particles with the particle size of more than 25 mu m is less than 100 in each 100mL of washing liquid to obtain the silver sulfide-loaded ion exchange resin;
3) filling the ion exchange resin into a container, sealing and sterilizing the container, connecting the container into an infusion pipeline, taking the injection flowing through the container, and testing as follows:
| removal rate/%) | |
| Sulfite salt | 92.8 |
| Amino acids | 3.4 |
Example 2
A method for removing antioxidant sulfite in compound amino acid injection comprises the following steps:
1) taking acrylamide-methacrylic acid copolymer, putting the acrylamide-methacrylic acid copolymer into silver nitrate solution, slowly stirring for 6 hours, standing and soaking for 20 hours, taking out, washing with purified water until no free silver ions exist in washing liquid, and obtaining a composite microsphere precursor;
2) standing and soaking the composite microsphere precursor in a sodium thiosulfate solution for 1 hour, taking out after the reaction is finished, and washing with injection water until the number of particles with the particle size of 15-25 mu m is less than 200 and the number of particles with the particle size of more than 25 mu m is less than 100 in each 100mL of washing liquid to obtain the silver sulfide-polymer gel composite microsphere;
3) filling the silver sulfide-polymer gel composite microspheres into a container, sealing and sterilizing the container, connecting the container into an infusion pipeline, taking the injection flowing through the container, and testing as follows:
| removal rate/%) | |
| Sulfite salt | 90.3 |
| Amino acids | 4.0 |
From examples 1 and 2, it can be seen that the method provided in the present invention can effectively remove sulfite from the injection solution.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention.
Claims (6)
1. A method for removing antioxidant sulfite in compound amino acid injection is characterized in that silver sulfide microspheres or ion exchange resin loaded with silver sulfide are used as an adsorbent after being sterilized so as to adsorb and remove sulfite in the compound amino acid injection.
2. The method for removing the antioxidant sulfite in the compound amino acid injection as claimed in claim 1, wherein the silver sulfide microspheres are one or more of hollow silver sulfide microspheres or silver sulfide-polymer gel composite microspheres.
3. The method for removing sulfite as an antioxidant in compound amino acid injection as claimed in claim 2, wherein the polymer gel is acrylamide, methacrylic acid, acrylic acid, methacrylate and derivatives thereof or copolymers of acrylate and derivatives thereof.
4. The method for removing sulfite as an antioxidant in compound amino acid injection as claimed in claim 3, wherein the polymer gel is one of acrylamide-methacrylic acid copolymer, acrylamide-n-butyl methacrylate copolymer and acrylamide-methyl methacrylate copolymer.
5. The method for removing sulfite as an antioxidant in compound amino acid injection as claimed in claim 1, wherein the ion exchange resin is porous cation exchange resin.
6. The method for removing sulfite as an antioxidant in compound amino acid injection as claimed in claim 5, wherein the cation exchange resin is one of styrene, methacrylate, cellulose, agarose or polyvinyl alcohol exchange resins.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110678096.7A CN113413927A (en) | 2021-06-18 | 2021-06-18 | Method for removing antioxidant sulfite in compound amino acid injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110678096.7A CN113413927A (en) | 2021-06-18 | 2021-06-18 | Method for removing antioxidant sulfite in compound amino acid injection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113413927A true CN113413927A (en) | 2021-09-21 |
Family
ID=77789127
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110678096.7A Pending CN113413927A (en) | 2021-06-18 | 2021-06-18 | Method for removing antioxidant sulfite in compound amino acid injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113413927A (en) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120073439A1 (en) * | 2010-09-24 | 2012-03-29 | Conocophillips Company | Supported silver sulfide sorbent |
| CN105460971A (en) * | 2015-12-10 | 2016-04-06 | 江南大学 | Controllable preparation method for micron-size columnar silver sulfide array |
| CN105722966A (en) * | 2013-10-02 | 2016-06-29 | J·R·科耐基 | Method for the selective removal of sulfites from beverages and modular apparatus for same |
| CN105819496A (en) * | 2016-03-21 | 2016-08-03 | 内江师范学院 | Preparation method of hollow nano silver sulfide microsphere |
| CN108728322A (en) * | 2017-04-19 | 2018-11-02 | 张茜 | A method of removing sulfur dioxide or sulphite in red wine |
| CN110860271A (en) * | 2019-12-28 | 2020-03-06 | 合肥学院 | SiO (silicon dioxide)2/Ag2Application of S nano composite powder in removing methylene blue |
| CN111603442A (en) * | 2020-06-04 | 2020-09-01 | 费森尤斯卡比华瑞制药有限公司 | Fat emulsion, compound amino acid and glucose injection and preparation method thereof |
| CN111921565A (en) * | 2020-08-25 | 2020-11-13 | 山东威高药业股份有限公司 | Method for reducing aluminum content in amino acid injection |
-
2021
- 2021-06-18 CN CN202110678096.7A patent/CN113413927A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120073439A1 (en) * | 2010-09-24 | 2012-03-29 | Conocophillips Company | Supported silver sulfide sorbent |
| CN105722966A (en) * | 2013-10-02 | 2016-06-29 | J·R·科耐基 | Method for the selective removal of sulfites from beverages and modular apparatus for same |
| CN105460971A (en) * | 2015-12-10 | 2016-04-06 | 江南大学 | Controllable preparation method for micron-size columnar silver sulfide array |
| CN105819496A (en) * | 2016-03-21 | 2016-08-03 | 内江师范学院 | Preparation method of hollow nano silver sulfide microsphere |
| CN108728322A (en) * | 2017-04-19 | 2018-11-02 | 张茜 | A method of removing sulfur dioxide or sulphite in red wine |
| CN110860271A (en) * | 2019-12-28 | 2020-03-06 | 合肥学院 | SiO (silicon dioxide)2/Ag2Application of S nano composite powder in removing methylene blue |
| CN111603442A (en) * | 2020-06-04 | 2020-09-01 | 费森尤斯卡比华瑞制药有限公司 | Fat emulsion, compound amino acid and glucose injection and preparation method thereof |
| CN111921565A (en) * | 2020-08-25 | 2020-11-13 | 山东威高药业股份有限公司 | Method for reducing aluminum content in amino acid injection |
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| 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 | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Li Qingkai Inventor after: Li Han Inventor after: Liu Hong Inventor after: Sun Haixia Inventor before: Li Han Inventor before: Liu Hong Inventor before: Sun Haixia |
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| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210921 |