CN106265499A - A kind of compound potassium dihydrogn phosphate pharmaceutical composition - Google Patents

A kind of compound potassium dihydrogn phosphate pharmaceutical composition Download PDF

Info

Publication number
CN106265499A
CN106265499A CN201610831541.8A CN201610831541A CN106265499A CN 106265499 A CN106265499 A CN 106265499A CN 201610831541 A CN201610831541 A CN 201610831541A CN 106265499 A CN106265499 A CN 106265499A
Authority
CN
China
Prior art keywords
pharmaceutical composition
preparation
water
potassium dihydrogen
compositions
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
Application number
CN201610831541.8A
Other languages
Chinese (zh)
Inventor
吴媛媛
吴旭杰
张瑜
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pharmaceutical Co Ltd Tianjin Jin Yao
Original Assignee
Pharmaceutical Co Ltd Tianjin Jin Yao
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Pharmaceutical Co Ltd Tianjin Jin Yao filed Critical Pharmaceutical Co Ltd Tianjin Jin Yao
Priority to CN201610831541.8A priority Critical patent/CN106265499A/en
Publication of CN106265499A publication Critical patent/CN106265499A/en
Pending legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/08Solutions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/42Phosphorus; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner

Abstract

A kind of pharmaceutical composition, is made up of 217 218g potassium dihydrogen phosphates, 319 320g dipotassium hydrogen phosphates and the water as adjuvant as active component in every 1000ml, it is characterized in that the oxygen content in compositions is at below 2mg/L.

Description

A kind of compound potassium dihydrogn phosphate pharmaceutical composition
Technical field:
The present invention relates to a kind of be made up of potassium dihydrogen phosphate, dipotassium hydrogen phosphate and the water as adjuvant as active component Pharmaceutical composition and preparation method thereof.
Background technology:
The injectable pharmaceutical compositions being made up of potassium dihydrogen phosphate, dipotassium hydrogen phosphate, is mainly used in total parenteral nutrition and treats As the supplement of phosphorus in method, as medium above operation or other wounds need the phosphorus supplement of more than 5 days patients of fasting, as various The multiple chronic disease patients such as operation and wounded patient, cardiovascular and cerebrovascular vessel, hepatopathy;Also can be used for some disease institute to hypophosphatemia.
Kong Xiangwen (disodium hydrogen phosphate and the mensuration respectively of potassium dihydrogen phosphate, Nanjing Medical College in mixed phosphate saline injection 19 88 years the 2nd phases of volume 8 of journal, 173-174 page) report that rod closes phosphate injection and has another name called sodium phosphate injection, it is loaded in " first All hospital preparation compilation " and " preparation handbook " in, its prescription is disodium hydrogen phosphate (being equivalent to anhydrous product 5.75 9) and di(2-ethylhexyl)phosphate Hydrogen potassium (anhydrous product 1.309), adds jetting and makes to 100.0ml.This product supplements phosphorus and treatment calcium, potassium, phosphorus generation for intravenous nutrition Thank disorder, the hypercalcemia that Vitamin D excess causes.
The invention of Application No. CN201010208559.5 relates to the production method of a kind of compound potassium dihydrogn phosphate, depends on Secondary including dispensing, decolouring, embedding, sterilizing, leak detection, lamp inspection, scald bottle, lettering and packaging step, described production method also includes After described embedding step, before described packaging step, described injection is carried out heating-cooling at least one times and processes, Described heating-cooling processes and refers to first be warming up to by injection 40 DEG C~100 DEG C, then gives free rein to be cooled to environment temperature Degree.Even if gained injection of the present invention runs into the environment of quenching or there will not be crystallization under low temperature storage environment, it is ensured that The quality of product and serviceability.But this patent only solves devitrification problem from technique, the most fundamentally solve to ask Topic.
The disclosure of the invention of the Application No. 201210331492.3 Compornd Potassium Dihydrogen phos-phate drug regimen of a kind of injection Thing, this compound potassium dihydrogn phosphate is made up of potassium dihydrogen phosphate, dipotassium hydrogen phosphate trihydrate, calcium disodium edetate, and every contains There are potassium dihydrogen phosphate 435.4-870.8mg, dipotassium hydrogen phosphate trihydrate 487.7-975.4mg in terms of dipotassium hydrogen phosphate, according to ground Acid calcium sodium 1-2mg, water for injection adds to 2L-4L.Its preparation method is: taking recipe quantity water for injection 70%, temperature is at 70-80 DEG C, add the calcium disodium edetate of recipe quantity, after stirring and dissolving;The potassium dihydrogen phosphate and the dipotassium hydrogen phosphate three that add recipe quantity are hydrated Thing is in terms of dipotassium hydrogen phosphate, and stirring is to dissolving completely;Record original ph, according to original ph, with 4% sodium hydroxide solution and 10% phosphoric acid solution regulation pH value range is at 5.5-6.5;To adding medicinal charcoal, stirring;Sucking filtration, adds water for injection to full dose, Mix homogeneously;Fine straining;Fill;Sterilizing;Lamp inspection;Warehouse-in;Obtain compound potassium dihydrogn phosphate.This Compornd Potassium Dihydrogen phos-phate medicine group Compound photostability is good, will not produce crystallization, clarity, good stability, and this invention, to improving product yield, reduces cost, Realize industrialization, be preferably applied to clinic, there is more obvious advantage.
The most never find that reducing oxygen content has a certain impact for stability tool.
Summary of the invention:
By long-term test, we have surprisingly found that, by the 217-218g phosphoric acid as active component in every 1000ml The pharmaceutical composition that potassium dihydrogen, 319-320g dipotassium hydrogen phosphate and the water as adjuvant form, when the oxygen content in compositions exists During below 2mg/L, photostability is good, runs into the environment of quenching or there will not be crystallization under low temperature storage environment.
A kind of pharmaceutical composition, by as the 217-218g potassium dihydrogen phosphate of active component, 319-320g in every 1000ml Dipotassium hydrogen phosphate and the water as adjuvant form, and it is characterized in that the oxygen content in compositions is at below 2mg/L.
The preparation method of aforementioned pharmaceutical compositions, is characterized in that the water of compositions cumulative volume more than 60% is put into container In, after addition potassium dihydrogen phosphate, dipotassium hydrogen phosphate are the most molten, it are cooled to 5-10 DEG C, then heat to 80-90 DEG C, be then cooled to Room temperature, then weigh in 0.3% medicinal charcoal addition container, stir evenly, decarbonization filtering, mend and add water to full dose, stir, be passed through nitrogen Rear fill.
Above-mentioned preparation method, it is characterized in that adding water to benefit after full dose again by medicinal liquid through 0.22 μm filter element filtering.
Above-mentioned preparation method, keeps after it is characterized in that fill carrying out sterilizing in 15 minutes under the conditions of 120~125 DEG C.
Above-mentioned preparation method, it is characterised in that make the oxygen content in compositions at below 2mg/L after being passed through nitrogen.
Above-mentioned pharmaceutical composition, it is characterised in that route of administration is to enter internal by injection.
In the present invention, dipotassium hydrogen phosphate, potassium dihydrogen phosphate can be corresponding hydrates, but corresponding hydrate is all with it In dipotassium hydrogen phosphate, potassium dihydrogen phosphate calculate.
Detailed description of the invention
Embodiment 1
Prescription:
Composition Embodiment 1-1 Embodiment 1-2 Embodiment 1-3
Potassium dihydrogen phosphate (g) 2170 2177 2180
Dipotassium hydrogen phosphate (g) 3190 3195 3200
Water for injection adds to (ml) 10000 10000 10000
Oxygen content (mg/L) 1.53 1.03 1.95
Preparation method:
Putting in container by the water of cumulative volume more than 60%, the addition potassium dihydrogen phosphate of recipe quantity, dipotassium hydrogen phosphate are the most molten After, it is cooled to 5-10 DEG C, then heats to 80-90 DEG C, be then cooled to room temperature, then weigh in 0.3% medicinal charcoal addition container, Stir evenly, decarbonization filtering, mend and add water to full dose, then by medicinal liquid through 0.22 μm filter element filtering, stir, be passed through nitrogen and make compositions In oxygen content fill after below the 2mg/L.Keep after fill carrying out sterilizing in 15 minutes under the conditions of 120~125 DEG C.
Comparative examples 1
Prescription:
Composition Comparative examples 1-1 Comparative examples 1-2 Comparative examples 1-3
Potassium dihydrogen phosphate (g) 2170 2177 2180
Dipotassium hydrogen phosphate (g) 3190 3195 3200
Water for injection adds to (ml) 10000 10000 10000
Oxygen content (mg/L) 3.71 2.19 7.52
Preparation method:
Putting in container by the water of cumulative volume more than 60%, the addition potassium dihydrogen phosphate of recipe quantity, dipotassium hydrogen phosphate are the most molten After, it is cooled to 5-10 DEG C, then heats to 80-90 DEG C, be then cooled to room temperature, then weigh in 0.3% medicinal charcoal addition container, Stir evenly, decarbonization filtering, mend and add water to full dose, then by medicinal liquid through 0.22 μm filter element filtering, stir, comparative examples 1-1 and 1-2 is passed through nitrogen, and comparative examples 1-3 is not passed through nitrogen, fill.Keep entering for 15 minutes after fill under the conditions of 120~125 DEG C Row sterilizing.
Comparative examples 2
Prescription:
Composition Comparative examples 2-1 Comparative examples 2-2 Comparative examples 2-3
Potassium dihydrogen phosphate (g) 2000 2100 2300
Dipotassium hydrogen phosphate (g) 3000 3300 3500
Water for injection adds to (ml) 10000 10000 10000
Oxygen content (mg/L) 1.81 1.23 1.87
Preparation method:
Putting in container by the water of cumulative volume more than 60%, the addition potassium dihydrogen phosphate of recipe quantity, dipotassium hydrogen phosphate are the most molten After, then weigh in 0.3% medicinal charcoal addition container, stir evenly, decarbonization filtering, mend and add water to full dose, then medicinal liquid is filtered through 0.22 μm Core filters, and stirs, is passed through nitrogen, fill.Keep after fill carrying out sterilizing in 15 minutes under the conditions of 120~125 DEG C.
Test example 1 stability contrast experiment
Each 20 batches are prepared respectively according to the method for embodiment 1, comparative examples 1,2.It is divided into 1 group at random by every 10 batches, point Do not carry out high temperature, illumination experiment, visual observations experimental result.
1.1 high temperature experiments:
Being placed 30 days in 60 DEG C of thermostatic drying chambers by sample, observe color sample and transparency, result is as follows.
.2 illumination experiment:
Being placed 30 days in 60 DEG C of thermostatic drying chambers by sample, light irradiates 30d (intensity 3 000lx), observes sample Color and transparency, result is as follows.

Claims (6)

1. a pharmaceutical composition, by as the 217-218g potassium dihydrogen phosphate of active component, 319-320g phosphorus in every 1000ml Acid hydrogen dipotassium and the water as adjuvant form, and it is characterized in that the oxygen content in compositions is at below 2mg/L.
2. a preparation method for the pharmaceutical composition described in claim 1, is characterized in that compositions cumulative volume more than 60% Water put in container, add potassium dihydrogen phosphate, dipotassium hydrogen phosphate the most molten after, be cooled to 5-10 DEG C, then heat to 80-90 DEG C, then it is cooled to room temperature, then weighs in 0.3% medicinal charcoal addition container, stir evenly, decarbonization filtering, mend and add water to full dose, stirring Uniformly, fill after nitrogen it is passed through.
3. the preparation method described in claim 2, filters medicinal liquid through 0.22 μm after it is characterized in that benefit adds water to full dose again Core filters.
4. the preparation method described in claim 2, keeps 15 minutes after it is characterized in that fill under the conditions of 120~125 DEG C Carry out sterilizing.
5. preparation method as claimed in claim 2, it is characterised in that make the oxygen content in compositions at 2mg/L after being passed through nitrogen Below.
6. the pharmaceutical composition described in a claim 1, it is characterised in that route of administration is to enter internal by injection.
CN201610831541.8A 2016-09-18 2016-09-18 A kind of compound potassium dihydrogn phosphate pharmaceutical composition Pending CN106265499A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610831541.8A CN106265499A (en) 2016-09-18 2016-09-18 A kind of compound potassium dihydrogn phosphate pharmaceutical composition

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610831541.8A CN106265499A (en) 2016-09-18 2016-09-18 A kind of compound potassium dihydrogn phosphate pharmaceutical composition

Publications (1)

Publication Number Publication Date
CN106265499A true CN106265499A (en) 2017-01-04

Family

ID=57711547

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610831541.8A Pending CN106265499A (en) 2016-09-18 2016-09-18 A kind of compound potassium dihydrogn phosphate pharmaceutical composition

Country Status (1)

Country Link
CN (1) CN106265499A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108619091A (en) * 2018-06-12 2018-10-09 南京正科医药股份有限公司 A kind of compound potassium dihydrogn phosphate
WO2020081118A1 (en) * 2018-10-19 2020-04-23 Cmp Development Llc Potassium phosphates composition for injection

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010046917A2 (en) * 2008-10-13 2010-04-29 Intas Pharmaceuticals Limited Fludarabine phosphate composition
CN101926761A (en) * 2010-06-23 2010-12-29 苏州天马医药集团天吉生物制药有限公司 Production method of compound potassium dihydrogn phosphate
CN102813675A (en) * 2012-09-07 2012-12-12 天津市嵩锐医药科技有限公司 Compound potassium hydrogen phosphate medicine combination for injection

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010046917A2 (en) * 2008-10-13 2010-04-29 Intas Pharmaceuticals Limited Fludarabine phosphate composition
CN101926761A (en) * 2010-06-23 2010-12-29 苏州天马医药集团天吉生物制药有限公司 Production method of compound potassium dihydrogn phosphate
CN102813675A (en) * 2012-09-07 2012-12-12 天津市嵩锐医药科技有限公司 Compound potassium hydrogen phosphate medicine combination for injection

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
国家药典委员会: "《中华人民共和国药典 第4部》", 30 June 2015 *
李威,等: "《药剂学》", 28 February 2014, 湖北科学技术出版社 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108619091A (en) * 2018-06-12 2018-10-09 南京正科医药股份有限公司 A kind of compound potassium dihydrogn phosphate
CN108619091B (en) * 2018-06-12 2020-10-16 南京正科医药股份有限公司 Compound potassium hydrogen phosphate injection
WO2020081118A1 (en) * 2018-10-19 2020-04-23 Cmp Development Llc Potassium phosphates composition for injection
US10632150B1 (en) 2018-10-19 2020-04-28 Cmp Development Llc Potassium phosphates composition for injection

Similar Documents

Publication Publication Date Title
CN108853011B (en) Calcium gluconate-L-calcium lactate oral liquid and preparation method thereof
CN102225063B (en) Pantoprazole sodium composition for injection
CN101455631B (en) Meglumine cyclic adenosine injection and preparation technique thereof
CN103550143A (en) Preparation method of levetiracetam injection
CN105434373A (en) Oxiracetam freeze-drying preparation for injection and preparation method thereof
CN106265499A (en) A kind of compound potassium dihydrogn phosphate pharmaceutical composition
CN106822175A (en) A kind of sodium acid carbonate ringer's injection and preparation method thereof
CN103126978A (en) Preparing method for ambroxol hydrochloride injection
CN102525905A (en) Tinidazole and sodium chloride injection and preparation method thereof
CN102552186A (en) Pantoprazole sodium freeze-dried powder injection and preparation method thereof
CN102302502A (en) Compound glycyrrhizin preparation and preparation method thereof
CN107157925A (en) Aramine parenteral solution and preparation method thereof
CN103301062A (en) Medium and long-chain lipid emulsion injection preparation method
CN1399959A (en) Etomidate fatty emulsion injection preparation method
CN101417105B (en) Zedoary turmeric oil glucose injection and preparation method thereof
CN104606209A (en) Compound vitamin medicine composition for injection and preparation method of compound vitamin medicine composition
CN103191431A (en) Coenzyme Q10 sodium chloride injection uneasy to crystallize and preparation method thereof
CN101244070A (en) Polyene phosphatidylcholine high-capacity injection
CN103371966A (en) Lobeline hydrochloride injection and preparation technology thereof
CN108210451B (en) Stable breviscapine injection and preparation process thereof
CN103432086A (en) Pemetrexed disodium freeze-dried powder injection for injection and preparation method thereof
CN102772373B (en) A kind of injection vinorelbine tartrate injectable powder and preparation method thereof
CN103239396B (en) Sodium ibandronate injection composition and preparation method of sodium ibandronate injection composition
CN102247381A (en) VitaminD2-and-vitaminE-containing medicinal composition for injection and preparation method thereof
CN106963779A (en) A kind of production method of compound potassium dihydrogn phosphate

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication

Application publication date: 20170104

RJ01 Rejection of invention patent application after publication