CN101912404A - Small-capacity injection containing four vitamins and preparation method thereof - Google Patents
Small-capacity injection containing four vitamins and preparation method thereof Download PDFInfo
- Publication number
- CN101912404A CN101912404A CN 201010244551 CN201010244551A CN101912404A CN 101912404 A CN101912404 A CN 101912404A CN 201010244551 CN201010244551 CN 201010244551 CN 201010244551 A CN201010244551 A CN 201010244551A CN 101912404 A CN101912404 A CN 101912404A
- Authority
- CN
- China
- Prior art keywords
- vitamin
- preparation
- injection
- tween
- vitamins
- 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
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a small-capacity injection containing four vitamins and a preparation method thereof. The small-capacity injection containing the four vitamins comprises the flowing components: vitamin A palmitate, a vitamin D2, a vitamin E, a vitamin K1, polysorbate 80 and polysorbate 20. The small-capacity injection containing the four vitamins is prepared by weighing a preparing amount of the components. The invention enables the product performance to be stable by adding a stabilizing agent and a latent solvent to a prescription; compared with the prior art, the product has the advantages of safety use, stable performance, determined curative effect and convenient use, and a sample of the product is stable and reliable as a result of animal experiments; and in addition, the preparation method is lower than a method for preparing a freeze-dry preparation and other dosage forms in production and preparation cost and saves the energy.
Description
Technical field
The present invention relates to a kind of compound recipe injection with small volume that contains vitamin and preparation method thereof.
Background technology
Vitamin A palmitate keeps amphiblestroid visual performance for promoting the neccessary composition of growth, and the stable effect of human cell membrane of keeping is arranged, and lacks that the back health stops growing, nyctalopia, xerophthalmia and keratomalacia.Vitamin D
2: form osseous tissue, increase the absorption of calcium and phosphorus, lack the back osteomalacia takes place.Vitamin E: the antioxidation of cell membrane, be oxygen free radical scavenger, make hematoclasis after the shortage and haemolysis, skeletal muscle and muscular degeneration of heart.Vitamin K
1: can form thrombinogen, it is normal to keep the blood coagulation function, causes prothrombin deficiency hemorrhage during shortage.
Can not need intestinal outer vitimin supplement A, D, E, K through the patient of the normal feed of digestive tract, because vitamin is unstable in aqueous solution usually, the compound vitamin performance of patient injection is difficult to stablize.Available technology adopting is made the method for lyophilized formulations and other dosage form, is mixed with injection during use and uses.The deficiency that exists is: manufacturing cost is higher, and does not have injection with small volume easy to use.
Summary of the invention
The object of the invention is to provide a kind of injection with small volume that contains four kinds of vitamin of safe in utilization, stable performance.
The object of the invention also is to provide the above-mentioned preparation method that contains the injection with small volume of four kinds of vitamin.
For reaching above-mentioned purpose, the present invention adopts following technical scheme:
It is as follows to contain each component weight in every 2ml solution:
Vitamin A palmitate 2250～2750IU
Vitamin D
2194～206IU
Vitamin E 15～16.5mg
Vitamin K
1.1.94～2.06mg
Tween-80 60～90mg
Tween-20 15～25mg
Preparation method:
Take by weighing vitamin A palmitate, the vitamin D of amount of preparation
2, vitamin E and vitamin K
1, Tween-80, Tween-20 stir after mixing, pour in the water for injection material-compound tank that fills amount of preparation about 90%, stirring and dissolving, with 5% sodium hydroxide adjusting pH value 6.0～6.5, back moisturizing stirs to full dose.Be filtered to clear and bright, fill production.
The present invention adds stabilizing agent in prescription, hydrotropy liquid makes properties of product stable.Compared with prior art, safe in utilization, the stable performance of product of the present invention, determined curative effect, easy to use.
In order to show effect of the present invention, the present invention's (claiming compound vitamin injection or compound vitamin injection (4) in the test) has been carried out following test:
Test one: the external hemolytic test of the present invention
One, test objective:
Observe the present invention tame rabbit erythrocyte is had or not haemolysis and cohesion.
Two, test material:
1, be subjected to the reagent thing: the present invention, specification: 2ml/ props up; Lot number: 20030801; Medicine pharmaceutcal corporation, Ltd provides by the sky, Hubei.Face with 50 times of preceding usefulness 0.9% sodium chloride injection dilutions.
2, tester: negative control thing: 0.9% sodium chloride injection; Positive control: distilled water.
3, the preparation of 2% red blood cell suspension:
By healthy rabbits cardiac puncture blood sampling 20ml, put into the triangular flask that fills sterile glass beads, stir blood with Glass rod, remove and defibrinate, make into defibrinated blood, 0.9% sodium chloride injection that adds 10 times of amounts, shake all, centrifugal, remove supernatant, sedimentary erythrocyte reuse 0.9% sodium chloride injection washing 2～3 times is till the apparent redness of supernatant.The gained erythrocyte is mixed with 2% suspension respectively with 0.9% sodium chloride injection, is for experiment.
Three, test method:
Get 12 in test tube, the according to the form below proportional quantity adds 2% red blood cell suspension and 0.9% sodium chloride injection of preparing with 0.9% sodium chloride injection successively, behind the mixing, in 37 ℃ of waters bath with thermostatic control 30 minutes, 1～No. 5 pipe adds sample stock solution respectively respectively then, 6～No. 10 pipe adds 50 times of diluents, and 11 negative control tube are managed positive control tube No. 12, make and respectively manage final volume and be 5ml, shake gently all, put in 37 ℃ of calorstats and be incubated, observe the haemolysis situation respectively at different time.(be transparent redness as solution, promptly represent haemolysis, as brownish red or reddish brown flocculent deposit are arranged in the solution, then expression has erythroagglutination).
Four, result of the test:
Observe at the appointed time, 2～No. 5 pipe engendered part haemolysis since 2 hours, No. 1 pipe and 6～No. 11 pipe supernatant liquid water white transparencies, and erythrocyte sinks gradually, does not see haemolysis, and No. 12 positive pipe liquid takes on a red color transparent.The results are shown in Table 1,2.
Table 1 hemolytic test result of the present invention (stock solution)
Table 2 hemolytic test result of the present invention (50 times of diluents)
Annotate: "-" be haemolysis not, "+" haemolysis, " ± " part haemolysis.
Five, conclusion:
When the present invention is stock solution, part haemolysis was arranged in the time of 2～4 hours, dilute 50 times after 0.1ml～0.5ml in 4h, erythrocyte is not had haemolysis and coacervation.
Experiment two: the present invention family's rabbit ear vein irritant test
One, test objective
Observe the present invention repeatedly intravenous administration to tame rabbit ear vein irritant reaction.
Two, test material
1, be subjected to the reagent thing: the present invention, specification: 2ml/ props up; Lot number: 20030801; Medicine pharmaceutcal corporation, Ltd provides by the sky, Hubei.
2, tester solvent control: 0.9% sodium chloride injection.
3, animal: white big ear rabbit, body weight 2.2～2.4kg, the male and female dual-purpose is provided by Hubei Province's Experimental Animal Center, the quality certification number: the moving word 19-009 of Hubei Province doctor.Single cage is raised, ad lib, and drinking-water, experiment is bought the last week.18～22 ℃ of laboratory temperatures; Humidity 55～75%.
Three, method and result
Get 3 of aforementioned animals, the intravenous injection the present invention that picks up the ears of every rabbit right, the left side ear vein is injected 0.9% sodium chloride injection, and volume injected is all the 10ml/ ear; Simulation clinical application speed instils at a slow speed.Once-a-day, successive administration 3 days was observed 1 hour before administration every day and after the administration, observe 24 hours internal stimulus situations after the last administration, with sacrifice of animal, cut rabbit ear edge vein proximal part from entry point 2.0cm～3.0cm part, 10% formalin fixed then with operating scissors, histopathologic slide checks, the result shows: of the present invention group of successive administration 3 days, and the visible vessels tube wall is complete under the mirror, and cell is clear, do not see other obvious abnormal changes, no necrosis or tissue degeneratiaon's reaction.There is not obvious pathology morphological differences with the contrast ear vein.
Four, conclusion
Continuous intravenous injection of the present invention 3 days does not see that aberrant angiogenesis changes, and pathological section shows: vascular tissue does not have necrosis and degeneration.
Under above-mentioned experiment condition, the result shows: after the rabbit vein administration of the present invention, compare with the contrast ear, do not have obvious pathomorphology difference.
Experiment three: Cavia porcellus hypersensitive test of the present invention
One, test objective:
Observe the anaphylaxis that the present invention causes Cavia porcellus through the whole body administration.
Two, test material:
1, be subjected to the reagent thing: the present invention, specification: 2ml/ props up; Lot number: 20030801; Medicine pharmaceutcal corporation, Ltd provides by the sky, Hubei.
2, tester: solvent control thing: 0.9% sodium chloride injection; Positive control: 10% albumin.
3, animal: 18 of Cavia porcelluss, body weight 250～350g, the male and female dual-purpose is provided by Hubei Province's medical experiment animal center, the animal quality certification number: 19-0010.The animal ad lib, drinking-water, experiment is bought the last week.18～22 ℃ of laboratory temperatures; Humidity 55～75%.
Three, test method:
Get above-mentioned Cavia porcellus, claim its body weight, animal is divided into 3 groups at random, the present invention, negative control group and positive controls, 6 every group by sex, body weight.Next day injection, every Cavia porcellus lumbar injection the present invention respectively, 0.9% sodium chloride injection, each 0.5ml/ of 10% albumin only, totally 3 times.The 14th day and 21 days sodium chloride after injection are first got 1/2 Cavia porcellus for every group, and intravenous injection the present invention respectively, 0.9% sodium chloride injection and 10% albumin 1ml/ only attack.
Four, observation index:
Observed 1 hour after the abdominal cavity sensitization administration, vein was observed 1 hour after attacking administration.Observed result.Judge by Cavia porcellus anaphylaxis progression whether tried thing qualified.The order of reaction reaches more than 2 grades and (comprises 2 grades), thinks that this is tried thing defective (seeing Table).
Cavia porcellus anaphylaxis level numerical table
Order of reaction reaction symptom
0 no significant reaction
1 has only and slightly grabs nose, trembles or perpendicular hair
2 have several times and cough, grab nose, tremble or perpendicular hair
More than 3 time or continuously cough, with dyspnea or spasm, tic etc.
4 spasm, tic, gatism, shock death
Five, result of the test:
1, sensitization is observed: the present invention, all Non Apparent Abnormality reactions after 0.9% sodium chloride injection and the 10% albumin group sensitization administration.
2, challenge trial:
Negative control group was attacked the back in the 14th day, 21 days and is observed and do not see and grab nose, tremble or anaphylaxis such as perpendicular hair after sensitization first, normally movable.The order of reaction is 0 grade.
Of the present invention group after attacking in the 14th day, obvious anaphylaxis does not all appear in 3 Cavia porcelluss, after attacking in the 21st day, obvious anaphylaxis does not take place in 3 Cavia porcelluss yet in addition, the order of reaction is 0 grade.
Positive controls the 14th day Cavia porcellus intravenous injection 10% albumin 1ml/ only after, spasm, tic all promptly appear, 2 Cavia porcellus death after about 1 minute; Above-mentioned identical reaction appears when injection in the 21st day.Positive controls is totally 4 Cavia porcellus death.The order of reaction is 4 grades.
Six, conclusion:
Under above-mentioned experimental condition, the present invention does not have obvious anaphylaxis to Cavia porcellus.
The present invention is through animal experiment, and the result is: hemolytic test does not produce haemolysis and cohesion; Irritant test is not seen the obvious stimulation reaction, and pathological section shows that vascular tissue does not have degeneration and necrosis; Hypersensitive test does not have obvious anaphylaxis.The present invention is safe in utilization effectively.
Preparation method of the present invention is lower than makes lyophilized formulations and other dosage form manufacturing cost, energy savings.
The specific embodiment
Embodiment 1
It is as follows to contain each component weight in every 2ml solution:
Vitamin A palmitate 2250IU
Vitamin D
2194IU
Vitamin E 15mg
Vitamin K
1.1.94mg
Tween-80 60mg
Tween-20 15mg
Process for preparation:
Take by weighing vitamin A palmitate, the vitamin D of amount of preparation
2, vitamin E and vitamin K
1, Tween-80, Tween-20 stir after mixing, pour in the water for injection material-compound tank that fills amount of preparation about 90%, stirring and dissolving, with 5% sodium hydroxide adjusting pH value 6.0～6.5, back moisturizing stirs to full dose.Be filtered to clear and bright, fill production.
Embodiment 2
It is as follows to contain each component weight in every 2ml solution:
Vitamin A palmitate 2750IU
Vitamin D
2206IU
Vitamin E 16.5mg
Vitamin K
1.2.06mg
Tween-80 90mg
Tween-20 25mg
Process for preparation:
Take by weighing vitamin A palmitate, the vitamin D of amount of preparation
2, vitamin E and vitamin K
1, Tween-80, Tween-20 stir after mixing, pour in the water for injection material-compound tank that fills amount of preparation about 90%, stirring and dissolving, with 5% sodium hydroxide adjusting pH value 6.0～6.5, back moisturizing stirs to 2ml.Be filtered to clear and bright, fill production.
Embodiment 3
It is as follows to contain each component weight in every 2ml solution:
Vitamin A palmitate 2250IU
Vitamin D
2194IU
Vitamin E 15mg
Vitamin K
11.94mg
Tween-80 90mg
Tween-20 25mg
Process for preparation:
Take by weighing vitamin A palmitate, the vitamin D of amount of preparation
2, vitamin E and vitamin K
1, Tween-80, Tween-20 stir after mixing, pour in the water for injection material-compound tank that fills amount of preparation about 90%, stirring and dissolving, with 5% sodium hydroxide adjusting pH value 6.0～6.5, back moisturizing stirs to full dose.Be filtered to clear and bright, fill production.
Embodiment 4
It is as follows to contain each component weight in every 2ml solution:
Vitamin A palmitate 2750IU
Vitamin D
2206IU
Vitamin E 16.5mg
Vitamin K
12.06mg
Tween-80 60mg
Tween-20 15mg
Process for preparation:
Take by weighing vitamin A palmitate, the vitamin D of amount of preparation
2, vitamin E and vitamin K
1, Tween-80, Tween-20 stir after mixing, pour in the water for injection material-compound tank that fills amount of preparation about 90%, stirring and dissolving, with 5% sodium hydroxide adjusting pH value 6.0～6.5, back moisturizing stirs to full dose.Be filtered to clear and bright, fill production.
It is as follows that sample under 1 of the treating excess syndrome example is investigated the result: accelerated test:
Get compound vitamin injection (4) sample listing packing, under 40 ℃ ± 2 ℃ conditions, placed 6 months, respectively at the 1st, 2,3, the sampling in June, carry out the detection of related item, the results are shown in following table (n=10).
Long term test:
Get compound vitamin injection (4) sample listing packing, under 25 ℃ ± 2 ℃ conditions, placed 36 months,, carry out the detection of related item, the results are shown in following table (n=50) respectively at sampling in the 3rd, 6,9,12,18,24,36 month.
By above four kinds of examples being quickened and long-time stability are investigated, the every before the deadline index of sample all meets legal national standard.
Claims (2)
1. injection with small volume that contains four kinds of vitamin is characterized in that:
It is as follows to contain each component weight in every 2ml solution:
Vitamin A palmitate 2250～2750IU
Vitamin D
2194～206IU
Vitamin E 15～16.5mg
Vitamin K
11.94～2.06mg
Tween-80 60～90mg
Tween-20 15～25mg
2. the described preparation method that contains the injection with small volume of four kinds of vitamin of claim 1 is characterized in that: the vitamin A palmitate, the vitamin D that take by weighing amount of preparation
2, vitamin E and vitamin K
1, Tween-80, Tween-20 stir after mixing, and pours in the water for injection material-compound tank that fills amount of preparation about 90% stirring and dissolving into, sodium hydroxide with 5% is regulated pH value 6.0～6.5, and back moisturizing stirs to full dose, be filtered to clear and bright, fill production.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010244551 CN101912404A (en) | 2010-01-30 | 2010-07-24 | Small-capacity injection containing four vitamins and preparation method thereof |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010105916.5 | 2010-01-30 | ||
| CN201010105916 | 2010-01-30 | ||
| CN 201010244551 CN101912404A (en) | 2010-01-30 | 2010-07-24 | Small-capacity injection containing four vitamins and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101912404A true CN101912404A (en) | 2010-12-15 |
Family
ID=43320153
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010244551 Pending CN101912404A (en) | 2010-01-30 | 2010-07-24 | Small-capacity injection containing four vitamins and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101912404A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103919718A (en) * | 2013-01-11 | 2014-07-16 | 沈阳兴齐眼药股份有限公司 | Vitamin A palmitate eye drop, preparation method and use thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101632679A (en) * | 2009-04-20 | 2010-01-27 | 邓盛齐 | Composite vitamin for injection and preparation method thereof |
-
2010
- 2010-07-24 CN CN 201010244551 patent/CN101912404A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101632679A (en) * | 2009-04-20 | 2010-01-27 | 邓盛齐 | Composite vitamin for injection and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 《国家药品标准》 20071231 国家药监局 《复方维生素注射液(4)》 157页 1-2 第75卷, 第1版 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103919718A (en) * | 2013-01-11 | 2014-07-16 | 沈阳兴齐眼药股份有限公司 | Vitamin A palmitate eye drop, preparation method and use thereof |
| CN103919718B (en) * | 2013-01-11 | 2016-12-28 | 沈阳兴齐眼药股份有限公司 | A kind of vitamin A palmitate eye drop and its production and use |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102309475B (en) | Levocarnitine for injection and preparation method thereof | |
| CN105687188B (en) | The pharmaceutical composition and its preparation method and application of prevention and/or treatment helminth | |
| CN102145164B (en) | IAPP (Islet Amyloid Polypeptide) analog injection with better stability | |
| CN101912404A (en) | Small-capacity injection containing four vitamins and preparation method thereof | |
| CN103110576A (en) | Lentinan injection preparation and preparation method thereof | |
| CN105963247A (en) | Preparation method of injection medicine for improving stability of quercetin medicine injection preparation | |
| CN104856946A (en) | High-safety dexamethasone sodium phosphate injection and preparation technology thereof | |
| CN109156545A (en) | A kind of composition and preparation method thereof with regulating blood lipid action | |
| CN102068408A (en) | Fasudil hydrochloride injection and preparation method thereof | |
| CN107157924A (en) | Naproxen sodium sodium chloride injection and preparation method thereof | |
| CN112999406A (en) | Anticancer medical glue and preparation method and application thereof | |
| CN116211901B (en) | Method for preparing brucea javanica oil composition and application thereof | |
| CN104688762A (en) | Medicinal composition containing 12 vitamins and used for intravenous injection | |
| CN100546585C (en) | Compound puerarin injection and preparation method thereof | |
| CN110408552A (en) | Se-enriched yeast is preparing the application in the antidote of liver renal toxicity caused by cinnabar | |
| DE60203895T2 (en) | USE OF N-ACETYL-D-GLUCOSAMINE IN THE MANUFACTURE OF A MEDICAMENT FOR SUPPRESSING THE SIDE EFFECTS OF RADIOTHERAPY AND CHEMOTHERAPY | |
| CN105769776A (en) | Freeze-dry composition for treating NHL (non-hodgkin lymphoma) and preparation method thereof | |
| CN106138211A (en) | A kind of medicinal composition for injections improving Radix Illicii Lanceolati drug injection preparation stability | |
| CN118453673A (en) | Method for preparing brucea javanica oil composition and application thereof | |
| CN1231216C (en) | Aspartic acid lomefloxacin powder and preparing method thereof | |
| CN107224428A (en) | Parenteral solution containing naproxen sodium and preparation method thereof | |
| CN102525959B (en) | Fat-soluble vitamin composition for injection and preparation method thereof | |
| CN106214711A (en) | Improve the preparation method of composition of Radix Et Caulis Acanthopanacis Senticosi drug injection preparation stability | |
| CN106176590A (en) | Improve the preparation method of quinidine sulfate ejection preparation stability composition | |
| CN106236840A (en) | Improve the preparation method of the pharmaceutical composition of Radix Illicii Lanceolati drug injection preparation stability |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20101215 |