CN117159460A - Preparation method of phosphorus supplement injection - Google Patents
Preparation method of phosphorus supplement injection Download PDFInfo
- Publication number
- CN117159460A CN117159460A CN202311210294.6A CN202311210294A CN117159460A CN 117159460 A CN117159460 A CN 117159460A CN 202311210294 A CN202311210294 A CN 202311210294A CN 117159460 A CN117159460 A CN 117159460A
- Authority
- CN
- China
- Prior art keywords
- phosphorus
- phosphorus supplement
- sodium
- injection
- preservative
- 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.)
- Pending
Links
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 title claims abstract description 59
- 229910052698 phosphorus Inorganic materials 0.000 title claims abstract description 59
- 239000011574 phosphorus Substances 0.000 title claims abstract description 59
- 239000013589 supplement Substances 0.000 title claims abstract description 46
- 239000007924 injection Substances 0.000 title claims abstract description 42
- 238000002347 injection Methods 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 39
- 239000008213 purified water Substances 0.000 claims abstract description 32
- 238000003756 stirring Methods 0.000 claims abstract description 20
- 239000003755 preservative agent Substances 0.000 claims abstract description 16
- 230000002335 preservative effect Effects 0.000 claims abstract description 16
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 15
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 15
- 238000001914 filtration Methods 0.000 claims abstract description 13
- 239000003381 stabilizer Substances 0.000 claims abstract description 13
- 239000003960 organic solvent Substances 0.000 claims abstract description 12
- 230000001954 sterilising effect Effects 0.000 claims abstract description 12
- 238000002156 mixing Methods 0.000 claims abstract description 11
- 238000005303 weighing Methods 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 8
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 33
- 239000001488 sodium phosphate Substances 0.000 claims description 33
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 33
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 claims description 26
- 229920000642 polymer Polymers 0.000 claims description 17
- 239000012528 membrane Substances 0.000 claims description 15
- 239000004695 Polyether sulfone Substances 0.000 claims description 13
- 229920006393 polyether sulfone Polymers 0.000 claims description 13
- XDIYNQZUNSSENW-UUBOPVPUSA-N (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O XDIYNQZUNSSENW-UUBOPVPUSA-N 0.000 claims description 12
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 8
- 239000003607 modifier Substances 0.000 claims description 7
- 229960004063 propylene glycol Drugs 0.000 claims description 7
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 6
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 6
- 235000013772 propylene glycol Nutrition 0.000 claims description 6
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 3
- 239000004472 Lysine Substances 0.000 claims description 3
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims description 2
- 239000004475 Arginine Substances 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 229940101006 anhydrous sodium sulfite Drugs 0.000 claims description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 2
- 238000005374 membrane filtration Methods 0.000 claims description 2
- 235000010241 potassium sorbate Nutrition 0.000 claims description 2
- 239000004302 potassium sorbate Substances 0.000 claims description 2
- 229940069338 potassium sorbate Drugs 0.000 claims description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 2
- 235000010234 sodium benzoate Nutrition 0.000 claims description 2
- 239000004299 sodium benzoate Substances 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 2
- 229940001584 sodium metabisulfite Drugs 0.000 claims description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims description 2
- 229940001474 sodium thiosulfate Drugs 0.000 claims description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 8
- 230000002421 anti-septic effect Effects 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 241001465754 Metazoa Species 0.000 description 26
- 238000012360 testing method Methods 0.000 description 20
- 239000000523 sample Substances 0.000 description 13
- RHCSKNNOAZULRK-APZFVMQVSA-N 2,2-dideuterio-2-(3,4,5-trimethoxyphenyl)ethanamine Chemical compound NCC([2H])([2H])C1=CC(OC)=C(OC)C(OC)=C1 RHCSKNNOAZULRK-APZFVMQVSA-N 0.000 description 11
- 239000003814 drug Substances 0.000 description 9
- 239000011148 porous material Substances 0.000 description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- 238000004925 denaturation Methods 0.000 description 5
- 230000036425 denaturation Effects 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 206010024769 Local reaction Diseases 0.000 description 4
- 230000001133 acceleration Effects 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000005286 illumination Methods 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 230000017074 necrotic cell death Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 230000008961 swelling Effects 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000007794 irritation Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 208000030212 nutrition disease Diseases 0.000 description 2
- 208000019180 nutritional disease Diseases 0.000 description 2
- 206010033675 panniculitis Diseases 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000008354 sodium chloride injection Substances 0.000 description 2
- SFEYIBBXGHFLAS-UHFFFAOYSA-N sodium;[4-(dimethylamino)-2-methylphenyl]-oxido-oxophosphanium Chemical compound [Na+].CN(C)C1=CC=C([P+]([O-])=O)C(C)=C1 SFEYIBBXGHFLAS-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 210000004304 subcutaneous tissue Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000019300 CLIPPERS Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 208000012239 Developmental disease Diseases 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 241000283977 Oryctolagus Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000035606 childbirth Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000021930 chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids Diseases 0.000 description 1
- 230000037326 chronic stress Effects 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 230000000091 immunopotentiator Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000009984 peri-natal effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- -1 phosphate compound Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 235000018648 unbalanced nutrition Nutrition 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The application relates to a preparation method of a phosphorus supplement injection, which comprises the following steps: weighing purified water and an organic solvent, adding a stabilizer and a phosphorus supplement, stirring until the purified water and the phosphorus supplement are completely dissolved, adding a preservative and an antioxidant, stirring and mixing uniformly, adjusting pH by an acid-base regulator, fixing the volume of the purified water to a fixed amount, filtering, and sterilizing to obtain the phosphorus supplement injection. The application fills the blank of the domestic phosphorus supplement injection, and has good process reproducibility and wide application prospect.
Description
Technical Field
The application relates to the field of veterinary medicines, in particular to a preparation method of a phosphorus supplement injection.
Technical Field
Under the conditions that epidemic diseases are increasingly complicated, the raising density is increased, and the nutrition and harmful ingredients of the feed are not completely controllable, various stress reactions and unbalanced nutrition become a key restriction point for restricting the continuous improvement of the raising benefit potential of the animal husbandry.
It is known that phosphorus is present in an animal in a large amount, and is a sixth element next to oxygen, carbon, hydrogen, nitrogen and sulfur, and occupies 1% of the weight. Bones are phosphorus-rich organs, and the phosphorus content in adults is about 600-700 mg, with 80-90% in bones. Extra-skeletal phosphorus also plays an important role in metabolism, and it is involved in the structural substances that make up living cells; participating in the synthesis and catabolism of almost all important organics; the high-energy phosphate compound plays an important role in the energy release, storage and utilization of the organism. In addition, phosphorus can exist in the form of H2P 03-or HP 03-in body fluids and be excreted outside the body via urine. Most of the phosphorus in blood exists in red blood cells in the form of organic phosphoric acid, and red blood cells also contain a small amount of inorganic phosphorus. The total phosphorus content in serum is about 14-15 mg/ml, wherein 5-8 mg is organic phosphorus.
Toldimifos sodium (Toldimfos sodium) is a nutritional supplement for supplementing phosphorus and has a molecular weight: 221.17, molecular formula: c (C) 9 H 13 NNaO 2 P, CAS number: 575-75-7. The chemical structural formula is as follows:
the traditional Chinese medicine composition is used for treating symptoms such as weakness, chronic stress, depression, mental fatigue and the like of human beings after operation and infection diseases in 1920. Sodium toldine is an ideal metabolism accelerator and immunopotentiator, and can be used for treating and preventing diseases related to childbirth and perinatal period, young livestock development and nutritional disorder, and the application field is still further expanded with the deep research.
As a phosphorus supplement, toldine sodium phosphate can improve metabolism, milk yield and fertility. Furthermore, the toldine sodium phosphate not only can act on skeletal muscle, but also can stimulate smooth muscle (uterine bladder), and has tonifying effect on cardiac muscle. And the toldine sodium phosphate has obvious regulating effect on acute and chronic metabolic disorders. Studies have shown that: the toldine sodium phosphate can be rapidly distributed in the tissue and absorbed, and discharged with urine within 24-36 hours. At the same time, it has a problem of being easily soluble in water, but extremely unstable in water. In conclusion, the development and application of the toldine sodium phosphate injection bring great economic and social benefits, and no technology of the toldine sodium phosphate injection is currently available at home.
Disclosure of Invention
Aiming at the restraint limitation of the technology, the application provides the preparation method of the phosphorus supplement injection, which not only expands the application of the toldine sodium phosphate, but also fills the blank of the domestic toldine sodium phosphate injection technology.
In order to achieve the above purpose, the present application adopts the following technical scheme:
the application provides a preparation method of a phosphorus supplement injection, which comprises the following steps:
weighing purified water and an organic solvent, adding a stabilizer and a phosphorus supplement, stirring until the components are completely dissolved, adding a preservative and an antioxidant, stirring and mixing uniformly, adjusting pH by an acid-base regulator, fixing the volume of the purified water to 100mL, filtering, and sterilizing to obtain the phosphorus supplement injection.
In some embodiments of the application, the filtration comprises membrane filtration.
In some embodiments of the application, the membrane comprises a polyethersulfone microporous filter membrane; wherein the aperture of the polyethersulfone microporous filter membrane is not more than 0.22 mu m.
In some embodiments of the application, the phosphorus supplement is toldine sodium phosphate.
In some embodiments of the application, the antioxidant is any one of anhydrous sodium sulfite, sodium metabisulfite, sodium thiosulfate, beta-D (+) glucose-glucose oxidase-catalase, wherein the mass ratio of the antioxidant to the phosphorus supplement is (0.1-1): 20; further, the antioxidant is beta-D (+) glucose-glucose oxidase-catalase, and the mass ratio of the antioxidant to the phosphorus supplement is (0.1-1): 20.
In some embodiments of the application, the organic solvent is any one of ethanol, isopropanol, polyethylene glycol, 1, 2-propanediol, preferably 1, 2-propanediol; wherein the mass ratio of the organic solvent to the phosphorus replenisher is (0.5-2) 1.
In some embodiments of the application, the preservative is any one of benzyl alcohol, sodium benzoate, phenethyl alcohol, potassium sorbate; wherein the mass ratio of the preservative to the phosphorus supplement is (0.1-1) 20; further, the preservative is phenethyl alcohol, and the mass ratio of the phenethyl alcohol to the phosphorus supplement is (0.5-1) 20; further, the preservative is benzyl alcohol, and the mass ratio of the benzyl alcohol to the phosphorus supplement is (0.1-0.5) 20; still further, if the preservative is a mixture of benzyl alcohol and phenethyl alcohol, then benzyl alcohol: phenethyl alcohol=1:1, the mass ratio of the mixture to phosphorus supplement is 1:20.
In some embodiments of the application, the acid-base modifier is any one of arginine, lysine, triethanolamine, sodium hydroxide and sodium carbonate, and the dosage of the acid-base modifier is to adjust the pH value to 9.0-12.0; further, the acid-base modifier is triethanolamine; further, the acid-base modifier is sodium hydroxide. Further, the pH was adjusted to 10-11.
In some embodiments of the application, the stabilizer comprises a polyamino acid-based polymer; further, the stabilizer comprises Apisolex TM Polymer。
Compared with the prior art, the application at least achieves the following technical effects:
(1) The toldine sodium is used as a nutritional supplement for improving diseases related to organism nutritional disorder and metabolism by utilizing the water solubility of toldine sodium, and the application range of toldine sodium in injection is greatly expanded.
(2) The stability of the toldine sodium phosphate injection under severe conditions (high temperature and illumination) is increased by adding the stabilizer, so that the toldine sodium phosphate injection can better exert the effect.
(3) By adding the antioxidant, the stability of the toldine sodium phosphate injection under severe conditions (warm and humid) is increased, and the preservation performance of the toldine sodium phosphate injection is improved.
(4) By controlling the mixed solution within a certain pH range, the irritation of the toldine phosphorus injection to animals can be reduced.
Detailed Description
The application provides a phosphorus supplement injection and a preparation method thereof.
The phosphorus supplement injection comprises: the phosphorus supplement agent comprises toldine sodium phosphate, a stabilizer, an organic solvent, a preservative, an antioxidant, an acid-base regulator and purified water. Wherein, the toldine sodium phosphate is a medicine component, is in powder form and is a commercial product; the toldine sodium phosphate is dissolved in pure water, and the stabilizer, the organic solvent and other auxiliary materials are added to increase the stability of the toldine sodium phosphate in water, so that the drug effect is ensured. The purified water and the organic solvent form a solvent together for dissolving the phosphorus supplement and other auxiliary materials; the antioxidant and the stabilizer act synergistically to ensure that the toldine sodium phosphate is stable and not decomposed in water and an organic solvent; because the main solvent of the injection is water, a preservative is needed to prevent the injection from putrefying long bacteria, and an acid-base regulator is needed to regulate the pH of the injection, reduce the irritation of the injection and make the injection milder for animals.
The preparation method of the phosphorus supplement injection comprises the steps of weighing purified water and an organic solvent, adding a stabilizer and a phosphorus supplement, stirring until the components are completely dissolved, adding a preservative and an antioxidant, stirring and mixing uniformly, regulating pH by an acid-base regulator, fixing the volume of the purified water to 100ml, filtering once by a polyether sulfone microporous filter membrane with the pore diameter of 0.22 mu m, and sterilizing to obtain the phosphorus supplement injection.
The present application will be described in further detail with reference to examples. The description is only intended to illustrate the application and is not intended to limit the scope of the application.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs, and the terms used herein in this description of the application are for the purpose of describing particular embodiments only and are not intended to be limiting of the application. Reagents and instruments used herein are commercially available, and reference to characterization means is made to the relevant description of the prior art and will not be repeated herein.
Example 1
Weighing 50g of purified water and 10g of ethanol, and adding Apisolex TM Stirring 1g of Polymer and 20g of toldine sodium phosphate until the Polymer and the toldine sodium phosphate are completely dissolved, adding 0.5g of phenethyl alcohol and 1g of beta-D (+) glucose-glucose oxidase-catalase, stirring and mixing uniformly, regulating pH to be 9 by lysine, fixing the volume of purified water to 100ml, filtering for one time by a polyether sulfone microporous filter membrane with the pore diameter of 0.22 mu m, and sterilizing to obtain the phosphorus supplement injection.
Example 2
50g of purified water and 10g of isopropanol were weighed and Apisolex was added thereto TM Stirring 1g of Polymer and 20g of toldine sodium phosphate until the Polymer and the toldine sodium phosphate are completely dissolved, adding 0.1g of benzyl alcohol and 0.5g of beta-D (+) glucose-glucose oxidase-catalase, stirring and mixing uniformly, adjusting pH to be 12 by sodium hydroxide, fixing the volume of purified water to 100ml, filtering the purified water once by a polyethersulfone microporous filter membrane with the pore diameter of 0.22 mu m, and sterilizing to obtain the phosphorus supplement injection.
Example 3
Weighing 30g of purified water and 20g of polyethylene glycol, and adding Apisolex TM And (3) stirring 1g of Polymer and 20g of toldine sodium phosphate until the Polymer and the toldine sodium phosphate are completely dissolved, adding 2g of sodium benzyl alcohol and 0.1g of beta-D (+) glucose-glucose oxidase-catalase, stirring and mixing uniformly, regulating the pH value to be 10 by triethanolamine, fixing the volume of purified water to 100ml, filtering the purified water through a polyether sulfone microporous filter membrane with the pore diameter of 0.22 mu m, and sterilizing the purified water to obtain the phosphorus supplement injection.
Example 4
50g of purified water and 15g of isopropanol were weighed and Apisolex was added TM Polymer 1g and toldine sodium phosphate 20g were stirred until complete dissolution, then benzyl alcohol 0.5g and beta-D (+) glucose-glucose oxidase-catalase 0.5g were addedStirring and mixing uniformly, adjusting pH to 11 by sodium hydroxide, fixing the volume of purified water to 100ml, filtering once by a polyethersulfone microporous filter membrane with the pore diameter of 0.22 mu m, and sterilizing to obtain the phosphorus supplement injection.
Example 5
50g of purified water and 20g of 1, 2-propanediol were weighed and Apisolex was added thereto TM 1g of Polymer and 20g of toldine sodium phosphate are stirred until complete dissolution, then 0.5g of benzyl alcohol, 0.5g of phenethyl alcohol and 0.5g of beta-D (+) glucose-glucose oxidase-catalase are added, the mixture is stirred and mixed uniformly, the pH value is regulated to be 11 by sodium hydroxide, the volume of purified water is fixed to 100ml, the purified water is filtered once through a polyethersulfone microporous filter membrane with the pore diameter of 0.22 mu m, and the phosphorus supplement injection is obtained after sterilization.
Example 6
Weighing 50g of purified water and 20g of 1, 2-propylene glycol, adding 20g of toldine sodium phosphate, stirring until the solution is completely dissolved, adding 0.5g of benzyl alcohol, 0.5g of phenethyl alcohol and 0.5g of beta-D (+) glucose-glucose oxidase-catalase, stirring and mixing uniformly, adjusting pH to be 11 by sodium hydroxide, fixing the volume of the purified water to 100ml, filtering for one time by a polyether sulfone microporous filter membrane with the pore diameter of 0.22 mu m, and sterilizing to obtain the phosphorus supplement injection.
Example 7
50g of purified water and 20g of 1, 2-propanediol were weighed and Apisolex was added thereto TM Stirring 1g of Polymer and 20g of toldine sodium phosphate until the Polymer and the toldine sodium phosphate are completely dissolved, adding 0.5g of benzyl alcohol and 0.5g of phenethyl alcohol, stirring and mixing uniformly, adjusting pH to be 11 by sodium hydroxide, fixing the volume of purified water to 100ml, filtering once by a polyether sulfone microporous filter membrane with the pore diameter of 0.22 mu m, and sterilizing to obtain the phosphorus supplement injection.
Example 8
Weighing 30g of purified water and 20g of polyethylene glycol, and adding Apisolex TM And (3) stirring 1g of Polymer and 20g of toldine sodium phosphate until the Polymer and the toldine sodium phosphate are completely dissolved, adding 2g of sodium benzyl alcohol and 0.1g of beta-D (+) glucose-glucose oxidase-catalase, stirring and mixing uniformly, regulating the pH value by triethanolamine to be 12.5, fixing the volume of purified water to 100ml, filtering the purified water through a polyethersulfone microporous filter membrane with the pore diameter of 0.22 mu m for one time, and sterilizing the purified water to obtain the phosphorus supplement injection.
Example 9
The samples of example 5 and example 6 were taken and stability of the influencing factors was investigated according to the guidelines of the "Chinese animal pharmacopoeia" one 9001.
The detection method comprises the following steps:
octadecylsilane chemically bonded silica is used as a filler for chromatographic conditions and system applicability tests; at 0.33% NaH 2 PO 4 Solution-acetonitrile-methanol (90:8:2) as mobile phase; the flow rate is 1.5ml per minute; the column temperature is 35 ℃; the detection wavelength was 270nm.
Taking a proper amount of the product by an assay method, precisely weighing, adding methanol for dissolving and quantitatively diluting to prepare a solution containing about 100 mug of toldine sodium phosphate in 1ml, taking the solution as a sample solution, precisely weighing 10 mug, injecting the solution into a liquid chromatograph, and recording a chromatogram; and taking a sodium toldine phosphate reference substance, and measuring by the same method. And measuring the relative density of the sample at the same time, converting the sample amount into milliliters, and calculating by a peak area according to an external standard method to obtain the product.
High temperature test: samples of examples 5 and 6 were taken, placed in an incubator at 60℃with an opening for 10 days, and sampled and tested on days 5 and 10.
Illumination test: samples of examples 5 and 6 were taken, placed in a suitable illumination box with an opening, and placed under an illumination of 4500 lx.+ -. 500lx for 10 days, and sampled and tested on days 5 and 10.
The results show that the sample of example 5 has good stability under high temperature and light conditions, and the sample of example 6 has poor stability.
Proof of no addition of the stabilizer Apisolex TM Polymer samples are less stable under severe conditions. Stabilizer Apisolex TM Polymer is an essential phosphorus supplement injection adjuvant.
Example 10
The samples of example 5 and example 7 were accelerated for one month under accelerated test conditions according to the guidelines of the "Chinese animal pharmacopoeia" one 9001. Acceleration conditions: the mixture was allowed to stand at 40.+ -. 2 ℃ and a relative humidity of 75.+ -. 5% for 1 month.
The results show that the sample of example 5 has good stability under acceleration for one month and the sample of example 6 has poor stability after acceleration for one month.
Samples without the addition of the antioxidant beta-D (+) glucose-glucose oxidase-catalase proved to be less stable after acceleration for 1 month. The antioxidant beta-D (+) glucose-glucose oxidase-catalase is a necessary phosphorus supplement injection adjuvant.
Example 11
The samples of example 3 and example 8 were taken and subjected to a stimulus test in strict compliance with the national drug administration (code 34, 2017, 9, 1) code of quality control of non-clinical study of drugs.
1. Test animals
8 healthy Japanese white rabbits (4/4) are taken. The samples were randomly divided into test sample groups (sample of administration example 8) and reference preparation groups (sample of administration example 3) according to gender and body weight, 4 samples were each, 2 male/2 female.
2. Administration of drugs
2.1 route of administration: subcutaneous injection.
2.2 methods of administration
An autologous left and right side control method is adopted.
The animal firstly uses electric hair clipper to cut hair, and exposes the skin at the left and right sides of shoulder blade, then uses aseptic operation method to make subcutaneous injection on the dehairing place at right (R) and left (L) sides of every rabbit respectively to administer test sample/reference preparation stock solution and sodium chloride injection with identical volume of 0.9%.
2.3 dosing concentration and dosing volume
The test article/reference preparation stock solution was administered to the administration side, and 0.9% sodium chloride injection was administered to the control side, with a volume of administration of 1 ml/side.
2.4 frequency of administration
The administration was carried out 1 time per day for 7 days.
3. Observation and measurement of various indexes of animal test
3.1 clinical symptoms and death Condition
Number of observations: clinical symptoms were observed once daily on the non-dosing day during the trial period and prior to dosing during the trial period.
The observation method comprises the following steps: the observation of the cage includes whether death, dying, activity, appearance, hair, trauma, faeces, etc.
3.2 body weight measurement
Number of measurements: before grouping animals
Example number: all surviving animals.
The measuring method comprises the following steps: peeling and weighing.
3.3 local symptom observation and result determination
The site of administration was observed 1 time a day (the day of administration was observed before administration) during the test period, and whether or not the administration caused a local reaction such as redness, congestion, exudation, denaturation or necrosis was observed, and the "local symptom observation Table" was filled.
CO was used 48h after the last dose for each group 2 1/2 animals were sacrificed (1 female/1 male) in each group euthanized. Skin and subcutaneous tissues were dissected, stimulus response conditions of the subcutaneous tissues at the injection site were visually observed, 10% neutral buffered formalin was fixed, and conventional tissue sections were subjected to histopathological examination.
The remaining animals were observed for a further 14 days, after the end of the observation period, using CO 2 The remaining animals were euthanized for anesthesia and again subjected to a pathology examination to understand the condition and degree of reversibility of the stimulatory response.
4. Test results:
animals generally had good status and no death occurred during the test period; the administration part is observed visually during the test period, the administration side of the animals in the test sample group is red and swollen, and no obvious abnormality is seen on the reference preparation group and the control side of all the animals.
The skin administration local subcutaneous part of the injection site of all animals on the administration side of the test sample group and the reference preparation group is observed visually after 48 hours of the last administration, and the control side has no local reactions such as red swelling, congestion, exudation, denaturation or necrosis; visual inspection of the section was continued for 14 days: the administration side and the control side of all animals in the reference preparation group have no local reactions such as red swelling, congestion, exudation, denaturation or necrosis, and the administration side and the control side of all animals in the test preparation group have no local reactions such as red swelling, congestion, exudation, denaturation or necrosis.
Histopathological examination results: 48 hours after the last administration, the administration side of the test sample group can see the drug-related histopathological change, local red swelling and denaturation reactions exist, and the control side of all animals does not see the drug-related histopathological change; no drug-related histopathological changes were seen on the dosing side for all animals of the reference formulation group and on the control side for all animals. The recovery was continued for 14 days, and no drug-related histopathological changes were seen on the dosing side of all animals in the test and reference formulation groups, and on the control side of all animals.
The test results show that: by regulating pH of injection to 10-11, the irritation factor of the medicinal preparation is reduced, and stress response of animals is reduced.
It is to be understood that the above-described embodiments are merely exemplary embodiments employed to illustrate the principles of the present application, however, the present application is not limited thereto, and thus is not intended to be limiting. Various changes, modifications, equivalents, improvements and modifications will occur to those skilled in the art without departing from the spirit and spirit of the application.
Claims (10)
1. A method for preparing a phosphorus supplement injection, which is characterized by comprising the following steps:
weighing purified water and organic solvent, adding stabilizer and phosphorus supplement, stirring until dissolving completely, adding antiseptic and antioxidant, stirring, mixing well, adjusting pH with acid-base regulator, constant volume, filtering, and sterilizing to obtain phosphorus supplement injection.
2. The pharmaceutical formulation of claim 1, wherein the filtration comprises membrane filtration.
3. The pharmaceutical formulation of claim 1, wherein the membrane comprises a polyethersulfone microporous filter membrane; wherein the aperture of the polyethersulfone microporous filter membrane is not more than 0.22 mu m.
4. The pharmaceutical formulation of claim 1, wherein the phosphorus supplement is toldine sodium phosphate.
5. The pharmaceutical formulation of claim 1, wherein the antioxidant is any one of anhydrous sodium sulfite, sodium metabisulfite, sodium thiosulfate, β -D (+) glucose-glucose oxidase-catalase; wherein the mass ratio of the antioxidant to the phosphorus supplement is (0.1-1) 20.
6. The pharmaceutical formulation according to claim 1, wherein the organic solvent is any one of ethanol, isopropanol, polyethylene glycol, 1, 2-propanediol, preferably 1, 2-propanediol; wherein the mass ratio of the organic solvent to the phosphorus replenisher is (0.5-2) 1.
7. The pharmaceutical formulation of claim 1, wherein the preservative is any one of benzyl alcohol, sodium benzoate, phenethyl alcohol, potassium sorbate; wherein the mass ratio of the preservative to the phosphorus supplement is (0.1-1) 20;
preferably, the preservative is phenethyl alcohol, and the mass ratio of the preservative to the phosphorus supplement is (0.5-1) 20;
preferably, the preservative is benzyl alcohol, and the mass ratio of the benzyl alcohol to the phosphorus supplement is (0.1-0.5) 20.
8. The pharmaceutical formulation of claim 7, wherein the preservative is further a mixture of benzyl alcohol and phenethyl alcohol; wherein the mixture comprises benzyl alcohol by mass: phenethyl alcohol=1:1, the mass ratio of the mixture to phosphorus supplement is 1:20.
9. The pharmaceutical preparation according to claim 1, wherein the acid-base modifier is any one of arginine, lysine, triethanolamine, sodium hydroxide and sodium carbonate, and the dosage is to adjust the pH to 9.0-12.0; preferably, the acid-base modifier is triethanolamine; preferably, the acid-base modifier is sodium hydroxide.
10. The pharmaceutical formulation of claim 1, wherein the stabilizer comprises a polyamino acid based polymer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311210294.6A CN117159460A (en) | 2023-09-19 | 2023-09-19 | Preparation method of phosphorus supplement injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311210294.6A CN117159460A (en) | 2023-09-19 | 2023-09-19 | Preparation method of phosphorus supplement injection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117159460A true CN117159460A (en) | 2023-12-05 |
Family
ID=88944900
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311210294.6A Pending CN117159460A (en) | 2023-09-19 | 2023-09-19 | Preparation method of phosphorus supplement injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117159460A (en) |
-
2023
- 2023-09-19 CN CN202311210294.6A patent/CN117159460A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102988291A (en) | Flurbiprofen axetil fat emulsion injection composition and preparation method thereof | |
| CN103690471A (en) | Pharmaceutical compositions and method for treating inflammation in cattle and other animals | |
| CN104474551B (en) | Melatonin phosphatide complexes, its Percutaneously administrable preparation and preparation method thereof | |
| CN104688721A (en) | Anti-rheumatoid arthritis drug gel containing paclitaxel liposome and preparation method of gel | |
| CN101791310A (en) | Vinpocetine medicine composition and preparation method thereof | |
| CN102657602B (en) | 3,5-dyhydroxyl-4-isopropyl diphenylethene chitosan gel and preparation method thereof | |
| CN102552137A (en) | Triptolide fat emulsion injection and preparation method thereof | |
| CN117159460A (en) | Preparation method of phosphorus supplement injection | |
| CN111514157A (en) | Application of composition in preparation of veterinary anti-parasitic drug, veterinary anti-parasitic transdermal solution and preparation method thereof | |
| Newman | Acquired tolerance to ethyl alcohol | |
| CN107693484A (en) | A kind of rifampin gel and preparation method thereof | |
| CN103181891A (en) | Andrographolide injection and preparation method thereof | |
| CN104274494B (en) | A kind of American cockroach external preparation and preparation method thereof | |
| CN110721152B (en) | Sustained-release composition for treating animal skin parasite and fungus infection | |
| CN106806376A (en) | The pharmaceutical composition of paracetamol and glycyrrhizic acid or its salt or derivatives thereof | |
| CN113662912B (en) | Marbofloxacin controlled-release gel for livestock and preparation method thereof | |
| CN104784200A (en) | Skin flap infection and avascular necrosis prevention and treatment transdermal preparation and preparation method thereof | |
| CN116919895A (en) | Thidiroxen injection and preparation method and application thereof | |
| DE102013107024A1 (en) | Methods and compositions for treating, modifying, and managing bone cancer pain | |
| CN103690496B (en) | Freeze-drying medicine composition containing sodium ozagrel | |
| CN107157921A (en) | Aescinate A, B lipidosome gels and preparation method thereof | |
| RU2765838C1 (en) | Remedy for the treatment of postpartum mastitis and endometritis in cows | |
| CN107126412A (en) | Aescinate B lipidosome gel and preparation method thereof | |
| CN106943339A (en) | Aescinate A lipidosome gel and preparation method thereof | |
| RU2238086C2 (en) | New medicinal formulation of n-(4-nitro-2-phenoxyphenyl)methanesulfonamide, method for its preparing and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |