CN102743394A - Composite fat-soluable vitamin injection - Google Patents
Composite fat-soluable vitamin injection Download PDFInfo
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- CN102743394A CN102743394A CN2012102650927A CN201210265092A CN102743394A CN 102743394 A CN102743394 A CN 102743394A CN 2012102650927 A CN2012102650927 A CN 2012102650927A CN 201210265092 A CN201210265092 A CN 201210265092A CN 102743394 A CN102743394 A CN 102743394A
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Abstract
The invention provides composite fat-soluable vitamin injection which is composed of the following raw materials: 0.5-1g of vitamin A palmitate, 0.001-0.005g of vitamin D2, 5-10g of vitamin E, 1.0+/-0.1g of vitamin K1, 50-80g of Solutol Hs 15 and proper amount of fat-soluable antioxygen. The fat-soluable vitamin injection can be totally placed under the normal-temperature and normal environment, can be always kept to be clear within the shelf life of the injection, and has no particles or phenomena of turbidity, layering and other unstable states.
Description
Technical field
The present invention relates to a kind of vitamin injection and method for preparing, particularly a kind of fatsoluble vitamin and preparation method thereof.
Background technology
Vitamin is a low-molecular-weight organic compound of keeping the necessary trace of body vital movement process.Its kind is a lot, and chemical constitution has nothing in common with each other, on physiology neither constitute the primary raw material of various tissues, neither intravital energy source, however it is in the reaction that energy produces and regulate in the body substance metabolism process and play crucial effect.
Different according to dissolubility, vitamin is divided into water solublity and fat-soluble two big classes.The vitamin that fatsoluble vitamin is meant is water insoluble, can store in vivo after absorbing, fatsoluble vitamin comprises vitamin A (retinol), vitamin D, vitamin E, vitamin K, the fatsoluble vitamin characteristics are: chemical composition is carbon containing, hydrogen, oxygen only; Be only soluble in fat and fat-soluble solvent; Absorb through lymphsystem with fat at intestinal, major part is stored in fatty tissue, is discharged on a small quantity by bile; Can accumulate at organs such as livers, excessive absorption can cause poisoning; Short-term lacks general physiochemical indice and can not check.When fatsoluble vitamin is taken in a large number,, can cause and accumulate over loading in the body and cause poisoning owing to discharge lessly.
Wherein retinoid is all very sensitive to air, ultraviolet and oxidant, and the catalytic action of high temperature and metal ion all can be quickened its decomposition, and the speed of vitamin A loss is influenced by enzyme, water activity, storage atmosphere and temperature; The vitamin D class is with vitamin D2 (ergocalciferol; Ergocalciferol) and vitamin D3 (cholecalciferol; Cholecalciferol) the most common, vitamin D2 is by the product of the ergosterol in yeast or the Ergota behind daylight or irradiation under ultraviolet ray, and can be absorbed by the body; Vitamin D3 is by the derivant that is stored in subcutaneous cholesterol (7-dehydrocholesterol), and transformation forms under irradiation under ultraviolet ray; To thermally-stabilised, but very responsive to oxygen, easy oxidation destroys vitamin E under oxygen free condition, and is also responsive to alkali and ultraviolet in addition.Naturally occurring vitamin K is a yellow oil, synthetic then be the yellow crystal powder; All K biostearins are heat resistanceheat resistant and water all, but subject to the destruction of acid, alkali, oxidant and light (special ultraviolet).
Because the body accumulation characteristics of fatsoluble vitamin are; Indexs such as short-term shortage human body blood are surveyed not come out, and cause poisoning in the body and accumulate for a long time, for this reason; Should as far as possible or must follow rational principle for this biostearin; Unsuitable blindly escalated dose should not be blured dosage, should not blur trap in the body.But; Be difficult for dissolving because fatsoluble vitamin the inside ingredient is clamminess again, especially water insoluble, the K biostearin is heat resistanceheat resistant and water all; Be prone to oxidized and destroyed by light (ultraviolet); General auxiliary agent such as cosolvent can't help it to be dissolved in water to become clear and bright solution, and therefore the antioxidant effect of antioxidant also dispatches a person meaning by force, when fatsoluble vitamin is prepared into injection liquid; Stability after raising dissolubility, the stability that does not therefore increase extra adjuvant, maintenance oxidizing component, the clear and bright solution of maintenance are placed is the major issue that needs solution.
Summary of the invention
The object of the invention is to disclose a kind of fatsoluble vitamin injection.Prior art more is a fatsoluble vitamin Emulsion, and the fat-soluble vitamin freeze-dried powder needle agent.Why producing this phenomenon, is because this area utilizes present known cosolvent, solubilizing agent etc., all can't solve the dissolving of fatsoluble vitamin and keep the difficult problem of clear and bright solution state.The invention provides the technical scheme that solves this difficult problem.
The present invention also aims to disclose the technology and the method for preparing of this fatsoluble vitamin injection.
The invention provides a kind of fatsoluble vitamin injection, it is characterized in that, the raw material of this injection consists of:
Vitamin A palmitate 0.5-1g,
Vitamin D2 0.001-0.005g,
Vitamin E 5-10g,
Vitamin K1 1.0 ± 0.1g,
Solutol?Hs15 50-80g，
Fat-soluble antioxidant is an amount of.
Above-mentioned fatsoluble vitamin injection products of the present invention has reached the environment held of room temperature normality fully, and in the normal shelf-life, this solution remains clear and bright state at injection, and no granule occurs, and does not have unsettled phenomenon such as muddiness, layering and takes place.Compared with present technology, product of the present invention has obtained amazing beneficial effect, compares with the product that the same industry is of the same type, has outstanding substantive distinguishing features and obvious improvement.
Preferably also contain the pH value of regulating this injection in the fatsoluble vitamin injection of the invention described above and be 5.5～7.0 pH regulator agent, more preferably contain the pH value of regulating injection and be 6.3～6.5 pH regulator agent.
The pH regulator agent that contains in the above-mentioned injection is preferably sodium hydroxide solution.
In a preferred embodiment of the present invention, a kind of fatsoluble vitamin injection is provided, its raw material consists of:
Vitamin A palmitate 0.65-0.85g,
Vitamin D2 0.002-0.003g,
Vitamin E 7-8g,
Vitamin K1 1.0 ± 0.1g,
Solutol?Hs15 55-75g，
Fat-soluble antioxidant is an amount of.
Above-mentioned fat-soluble antioxidant is antioxidant well known in the art, and its consumption is also in normal ranges.
Wherein, it is 5.5～7.0 pH regulator agent that above-mentioned composition preferably also contains the pH value of regulating this injection, more preferably contains the pH value of regulating injection and be 6.3～6.5 pH regulator agent.
In another preferred embodiment of the present invention, a kind of fatsoluble vitamin injection is provided, its raw material consists of:
Vitamin A palmitate 0.65-0.85g,
Vitamin D2 0.002-0.003g,
Vitamin E 7-8g,
Vitamin K1 1.0 ± 0.1g,
Solutol?Hs15 60-70g，
Fat-soluble antioxidant is an amount of.
Wherein, it is 5.5～7.0 pH regulator agent that above-mentioned composition preferably also contains the pH value of regulating this injection, more preferably contains the pH value of regulating injection and be 6.3～6.5 pH regulator agent.
In another preferred embodiment of the present invention, a kind of fatsoluble vitamin injection is provided, its raw material consists of:
Vitamin A palmitate 0.65-0.85g,
Vitamin D2 0.002-0.003g,
Vitamin E 7-8g,
Vitamin K1 1.0 ± 0.1g,
Solutol?Hs15 65±0.5g，
Fat-soluble antioxidant is an amount of.
Wherein, it is 5.5～7.0 pH regulator agent that above-mentioned composition preferably also contains the pH value of regulating this injection, more preferably contains the pH value of regulating injection and be 6.3～6.5 pH regulator agent.
In most preferred embodiment of the present invention, a kind of fatsoluble vitamin injection is provided, its raw material consists of:
Vitamin A palmitate 0.7352g,
Vitamin D2 0.0025g,
Vitamin E 7.5g,
Vitamin K1 1.0g,
Solutol?Hs15 65.0g，
Fat-soluble antioxidant is an amount of.
The fat-soluble antioxidant that the present invention adopts is antioxidant well known in the art, and the amount of the fat-soluble antioxidant that the present invention adopts is above-mentioned " in right amount ", is the reasonable volume of this area antioxidant in injection, and it is known consumption.This fat-soluble antioxidant is any or its mixing in Butylated hydroxyanisole, dibenzylatiooluene, polysorbate 20, the polyoxyethylene sorbitan monoleate; Be preferably the mixing of Butylated hydroxyanisole and dibenzylatiooluene, or the mixing of polysorbate 20 and polyoxyethylene sorbitan monoleate; Mixed proportion is 0.1: 1～and 1: 0.1, preferred 0.3: 1～1: 0.3; More preferably 0.5: 1～1: 0.5.
Above-mentioned composition preferably also contains the pH regulator agent that the pH value of regulating this injection is 5.5～7.0 (preferred 6.3～6.5).
The cosolvent of general solution through experiment showed, in product of the present invention, add after, though that product reaches is clear and bright; But place the back layering, be uneven Emulsion state in the shelf-life, in addition; For example the Tween 80 nephrotoxicity is big for some cosolvent, and is not suitable for product of the present invention.
The Solutol Hs15 that the present invention relates in full is the common name of " Polyethylene Glycol (PEG) lithium 12-hydroxy stearate ", and therefore, Solutol Hs15 is Polyethylene Glycol (PEG) lithium 12-hydroxy stearate.
One of novelty of the present invention is: adopted Solutol HS-15 to carry out the solubilising of fatsoluble vitamin; The preparation of processing is clear and bright uniform solution; Not Emulsion or microemulsion; Clear and bright uniform fatsoluble vitamin injection of the present invention has reached 2 years constant muddinesses of normal condition held, unsettled abnormal phenomenas such as layering do not occur.
But, the file report is arranged, experiment is proof also; Adopt the injection of Solutol HS-15 solubilising in pressure sterilizing, can become muddy (estimation has been covered with clouds) generally speaking, even stratified phenomenon occurs, cause the solution skewness and influenced the character of dispersion; The data of BASF shows and can obtain restoring and solving through jolting; Practical situation is so really, even layering, can make it reinstatement through jolting (or ultrasonic); But this is also infeasible on producing, and does not also meet science.Although report; The character that causes the solution skewness and influence dispersion can make solution obtain restoring through jolting; But product of the present invention need not jolting, need not to adopt similar Emulsion that kind to seek and makes it way restorative all extra property, complementary.The testing result of tracking test proves; Product of the present invention can reach fully that (in 3 years) solution keeps clear and bright state in the shelf-life; Unsettled phenomenons such as no granule appearance, no muddiness or layering; For the technological progress of fatsoluble vitamin injection provides technical support, and, the progress of advancing by leaps and bounds obtained on the technology platform before this.
The present invention also provides a kind of method for preparing of fatsoluble vitamin injection, and this method comprises:
(1), takes by weighing the water for injection of total dosing amount 50～80%, the alcoholic solution of preparation 150～200ml95%;
(2), vitamin D2 and fat-soluble antioxidant are added dissolve with ethanol, pour among the Solutol Hs15 of thawing mixing into;
(3), vitamin A palmitate, vitamin E, vitamin K1 are added in the solution of (2), stir to clarify;
(4), the water for injection of (1) is added in the clear solutions that (3) obtain mixing;
(5) in the solution that (4) obtain, add active carbon, decarburization filters then;
(6) adjust pH 6.3～6.5, again through filtering with microporous membrane, add the total dosing amount of injection water, promptly get.
Because of easy oxidation under the vitamin A palmitate room temperature, therefore, as the general stored refrigerated of raw material; It is solid under stored refrigerated, and is oxidized in order to avoid it to greatest extent, and the present invention adopts the ultrasonic method that makes its thawing; The contrast experiment proves; The degree of oxidation of this raw material vitamin A palmitate of the method for ultrasonic thawing is minimum, and therefore, ultrasonic method more is applicable to these article.
In experimentation, the inventor finds that also Solutol Hs15 need handle preceding the thawing more than 30 ℃ that feed intake, and it is more full and uniform to guarantee that like this itself and vitamins raw materials mix get, and the product each side index that finally obtains is optimum.
In the present invention, the adding mode of the described water for injection of step (4) for (refer to each addition addition) from less to more, the gradient type that (refers to adding speed) from fast to slow or gradual adding mode.
In a preferred embodiment of the invention, said method comprises:
(1) takes by weighing the water for injection of total dosing amount 50～80%, the alcoholic solution of preparation 150～200ml95%;
(2) vitamin D2 and fat-soluble antioxidant are added an amount of dissolve with ethanol, pour mixing among the Solutol Hs15 of thawing into;
(3) through ultrasonic it is melted vitamin A palmitate, again the A cetylate, vitamin E, the vitamin K1 that melt are added in the solution that (2) obtain, be stirred to into clear solutions;
(4) water for injection of (1) is added in the clear solutions that (3) obtain at least at twice mixing; The mode that this water for injection adds be addition from less to more, adding speed gradient type from fast to slow or gradual adding mode;
(5) in the solution that (4) obtain, add active carbon, decarburization filters then;
(6) adjust pH 6.3～6.5, again through filtering with microporous membrane, add the total dosing amount of injection water, promptly get.
The most significant advantage that the present invention and technology thereof are brought is; Solved the injection that adopts Solutol HS-15 solubilising in the industry and in pressure sterilizing, can become muddy (estimation has been covered with clouds); Even stratified phenomenon appears; Thereby the adverse effect of having avoided causing the solution skewness to greatest extent and having influenced the character of dispersion; And by this technologic slight improvement, for example: adding mode, the Solutol Hs15 of vitamin A palmitate ultrasonic thawing earlier, water for injection melt processing, low temperature sterilization etc. with temperature more than 30 ℃ before feeding intake, and have solved puzzlement vitamin D for a long time, the technical barrier that vitamin K sterilization front and back content sharply descends in the industry; Obtained accomplishing the injection of clear and bright, even, stable compound recipe fatsoluble vitamin, intending trade name is " compound injection (4) ".
Solutol.HS15 is a kind of Polyethylene Glycol (PEG) lithium 12-hydroxy stearate, and polyglycol distearate 15 is claimed Polyethylene Glycol-12-hydroxy stearic acid ester again, and physicochemical properties show at room temperature that outward appearance is light yellowish-white paste.1, the sub-fraction in the 2-hydroxyl family can be by the Polyethylene Glycol etherificate.The increase of the solubility with temperature in water and reducing.If be stored in 25 ℃, can guarantee 24 months stability.Experiment of the present invention shows that Solutol.HS15 can not occurred important properties by steam sterilization (121 ℃, 15 minutes) and change, and is a kind of low toxicity non-ionic surface active agent.But it is used for these article, comprehensive consideration, the method for the preferred low temperature sterilization of the present invention, for example membrane filtration.
Clinical usage: 1 of injection formulation of the present invention (2ml/ props up) is added in the transfusions such as 500ml glucose, sodium chloride, aminoacid intravenous drip.
Indication: product of the present invention belongs to vitamin drug, and being applicable to can not be through the patient of the normal feed of digestive tract, and the intestinal of vitamin A, D2, E, K1 replenishes outward.
Fatsoluble vitamin prescription of the present invention and craft screening experiment mainly are that indexs such as particulate matter, layering after solubility experiment, stability test, the placement are screened; Screening process and method are the screening method method of conventional injection; Experimental data slightly can provide experimental record to prove if need at any time.
Fatsoluble vitamin is one of indispensable ingredient of parenteral nutrition, in order to satisfy the physiological need of every day to enteric solubility vitamin A, vitamin D2, vitamin E, vitamin K1 of being grown up.Feed intake according to recipe quantity and to prepare the fatsoluble vitamin injection according to conventional method; Fatsoluble vitamin injection vitamin A, vitamin E, vitamin D2 and vitamin K1 before and after sterilization are carried out assay, and vitamin D2 and vitamin K1 content content after sterilization only is about 47.1% and 7.7% before sterilizing respectively as a result.
Two of innovative point of the present invention has been to solve the compound liposoluble vitamins problem that content sharply descends after sterilization.
The use of this area injection metal ion chelation agent (edetate) that especially fatsoluble vitamin class injection is commonly used is not obvious to suppressing vitamin D2 and vitamin K1 content decline effect; And produce other not clear related substances, health is caused adverse influence.Result of the test shows: adding 0.0025%～0.02% Ethylenedinitrilotetraacetic Acid acid calcium sodium as compound liposoluble vitamins injection stabilizing agent addition; Though can guarantee that the change before and after sterilization of vitamin D2 and vitamin K1 is in tolerance interval in the compound liposoluble vitamins injection; But experiment is also found: disodiumedetate can be combined into the minimizing that soluble complex causes calcium with calcium ion, uses disodiumedetate can cause blood calcium to descend in the intravenous formulations.
The present invention preferably resolves its effective ingredient (vitamin D2 and K1) structure in preparation and sterilization process and is prone to take place the problem that the oxidation generation causes content sharply to descend.Compositions of the present invention is owing to add the Solutol.HS15 of appropriate dose; It is suppressing the situation that vitamin D2 and vitamin K1 content before and after the sterilization sharply obviously are superior to not adding Solutol.HS15 aspect the decline, has the effect of vitamin D2 and the rapid decline of vitamin K1 content before and after the obvious suppression sterilization.Simultaneously; The compositions of the above-mentioned form of the present invention vitamin D2 and vitamin K1 content before and after to sterilization sharply descend obvious inhibitory action are being arranged, and can guarantee that all vitamin D2 remains unchanged in the front and back of sterilizing with vitamin K1 basically in the compound liposoluble vitamins injection.Thereby can reduce waste to raw material, reduced the patient owing to sharply decline and possibly produce the various unpredicted undesirable element that catabolite produces of vitamin D2 and vitamin K1 content before and after the sterilization.
Pharmaceutical composition of the present invention can solve its effective ingredient (vitamin D2, vitamin K1) preferably the problem that oxidation produces catabolite takes place in preparation and sterilization process, has guaranteed safety of clinical administration.
Get the fatsoluble vitamin injection of the present invention that an embodiment 1 prepares and be added among the 5 glucose injection 500ml, in 0,1,2,4,6,8 hour, investigate indexs such as clarity of solution, pH value, content.The result sees the following form:
The table embodiment 1 study on the stability result of fatsoluble vitamin injection of the present invention in glucose solution
Experimental result shows: embodiment 1 product each item index in glucose injection does not have significant change, and compatibility is stable.
(2) stability in sodium chloride injection
The same, add in the sodium chloride injection, in 0,1,2,3,4,5 hour, investigate indexs such as clarity of solution, pH value, content respectively.The result sees the following form.
The table embodiment 1 study on the stability result of fatsoluble vitamin injection of the present invention in sodium chloride solution
Get the fatsoluble vitamin injection of the present invention that an embodiment 2 prepares and be added in the sodium chloride injection, in 0,1,2,4,6,8 hour, investigate indexs such as clarity of solution, pH value, content respectively.The result sees the following form.
The study on the stability result of fatsoluble vitamin injection in sodium chloride solution of table embodiment 2
The pharmacological toxicology experiment of these article can be referring to the related request of the fat-soluble compound vitamin preparation of injection, and open file is a lot, and the experiment of the sudden peal of thunder is carried out with reference to those open source literatures, and the result shows that its toxicity is low, and drug effect is remarkable.Repeat no more at this.
The specific embodiment
With specific embodiment the present invention is further described below, but does not influence protection scope of the present invention.
Embodiment 1
A kind of fatsoluble vitamin injection, its raw material consists of:
Vitamin A palmitate 0.7352g,
Vitamin D2 0.0025g,
Vitamin E 7.5g,
Vitamin K1 1.0g,
SolutolHs15 65.0g，
Fat-soluble antioxidant is an amount of.
Method for preparing comprises:
(1) takes by weighing the water for injection of total dosing amount 50～80%, the alcoholic solution of preparation 150～200ml95%;
(2) vitamin D2 and fat-soluble antioxidant are added an amount of dissolve with ethanol, pour mixing among the Solutol Hs15 of thawing into;
(3) through ultrasonic it is melted vitamin A palmitate, again the A cetylate, vitamin E, the vitamin K1 that melt are added in the solution that (2) obtain, be stirred to into clear solutions;
(4) water for injection of (1) is added in the clear solutions that (3) obtain at least at twice mixing; The mode that this water for injection adds be addition from less to more, adding speed gradient type from fast to slow or gradual adding mode;
(5) in the solution that (4) obtain, add active carbon, decarburization filters then;
(6) adjust pH is about 6.4, again through filtering with microporous membrane, adds the total dosing amount of injection water, promptly gets.
Embodiment 2
A kind of fatsoluble vitamin injection, its raw material consists of:
Vitamin A palmitate 0.65g,
Vitamin D2 0.002g,
Vitamin E 7g,
Vitamin K1 1.0 ± 0.1g,
Solutol?Hs15 65±0.5g，
Fat-soluble antioxidant is an amount of.
Method for preparing comprises:
(1) takes by weighing the water for injection of total dosing amount 50～80%, the alcoholic solution of preparation 150～200ml95%;
(2) vitamin D2 and fat-soluble antioxidant are added an amount of dissolve with ethanol, pour mixing among the Solutol Hs15 of thawing into;
(3) vitamin A palmitate, vitamin E, vitamin K1 are added in the solution of (2), add the ethanol of surplus, stir to clarify;
(4) water for injection of (1) is added in the clear solutions that (3) obtain mixing;
(5) in the solution that (4) obtain, add active carbon, decarburization filters then;
(6) adjust pH 6.3～6.5, again through filtering with microporous membrane, add the total dosing amount of injection water, promptly get.
Embodiment 3
A kind of fatsoluble vitamin injection, its raw material consists of:
Vitamin A palmitate 0.85g,
Vitamin D2 0.003g,
Vitamin E 8g,
Vitamin K1 1.0 ± 0.1g,
SolutolHs15 65±0.5g，
Fat-soluble antioxidant is an amount of.
Method for preparing is with embodiment 1.
Embodiment 4
A kind of fatsoluble vitamin injection, its raw material consists of:
Vitamin A palmitate 0.75g,
Vitamin D2 0.0025g,
Vitamin E 7.5g,
Vitamin K1 1.0g,
SolutolHs15 70g，
Fat-soluble antioxidant is an amount of.
Method for preparing is with embodiment 1.
5 one kinds of fatsoluble vitamin injection of embodiment, its raw material consists of:
Vitamin A palmitate 0.75g,
Vitamin D2 0.0025g,
Vitamin E 7.5g,
Vitamin K1 1.0g,
SolutolHs15 55g，
Fat-soluble antioxidant is an amount of.
Method for preparing is with embodiment 1.
6 one kinds of fatsoluble vitamin injection of embodiment, its raw material consists of:
Vitamin A palmitate 0.75g,
Vitamin D2 0.0025g,
Vitamin E 7.5g,
Vitamin K1 1.0g,
SolutolHs15 75g，
Fat-soluble antioxidant is an amount of.
Claims (10)
1. a fatsoluble vitamin injection is characterized in that, the raw material of this injection consists of:
Vitamin A palmitate 0.5-1g,
Vitamin D2 0.001-0.005g,
Vitamin E 5-10g,
Vitamin K1 1.0 ± 0.1g,
SolutolHs15 50-80g，
Fat-soluble antioxidant is an amount of.
2. fatsoluble vitamin injection as claimed in claim 1 is characterized in that, the raw material of this injection consists of:
Vitamin A palmitate 0.65-0.85g,
Vitamin D2 0.002-0.003g,
Vitamin E 7-8g,
Vitamin K1 1.0 ± 0.1g,
SolutolHs15 55-75g，
Fat-soluble antioxidant is an amount of.
3. fatsoluble vitamin injection as claimed in claim 1 is characterized in that, the raw material of this injection consists of:
Vitamin A palmitate 0.65-0.85g,
Vitamin D2 0.002-0.003g,
Vitamin E 7-8g,
Vitamin K1 1.0 ± 0.1g,
SolutolHs15 60-70g，
Fat-soluble antioxidant is an amount of.
4. fatsoluble vitamin injection as claimed in claim 1 is characterized in that, the raw material of this injection consists of:
Vitamin A palmitate 0.65-0.85g,
Vitamin D2 0.002-0.003g,
Vitamin E 7-8g,
Vitamin K1 1.0 ± 0.1g,
SolutolHs15 65±0.5g，
Fat-soluble antioxidant is an amount of.
5. fatsoluble vitamin injection as claimed in claim 1 is characterized in that, the raw material of this injection consists of:
Vitamin A palmitate 0.7352g,
Vitamin D2 0.0025g,
Vitamin E 7.5g,
Vitamin K1 1.0g,
Solutol?Hs15 65.0g，
Fat-soluble antioxidant is an amount of.
6. like each described fatsoluble vitamin injection of claim 1-5, it is characterized in that described fat-soluble antioxidant is any or its mixing in Butylated hydroxyanisole, the dibenzylatiooluene.
7. fatsoluble vitamin injection as claimed in claim 6 is characterized in that, also contains the pH value of regulating this injection and be 5.5～7.0 pH regulator agent; This pH regulator agent is a sodium hydroxide solution.
8. the method for preparing of the described fatsoluble vitamin injection of claim 1 is characterized in that, this method comprises:
(1) takes by weighing the water for injection of total dosing amount 50～80%, the alcoholic solution of preparation 150～200ml95%;
(2) vitamin D2 and fat-soluble antioxidant are added an amount of dissolve with ethanol, pour mixing among the Solutol Hs15 of thawing into;
(3) vitamin A palmitate, vitamin E, vitamin K1 are added in the solution that (2) obtain, stir to clarify;
(4) water for injection of (1) is added in the clear solutions that (3) obtain mixing;
(5) in the solution that (4) obtain, add active carbon, decarburization filters then;
(6) adjust pH 6.3～6.5, again through filtering with microporous membrane, add the total dosing amount of injection water, promptly get.
9. method for preparing as claimed in claim 8 is characterized in that, said step (3) fully behind the mixing, adds the ethanol of surplus for vitamin A palmitate, vitamin E, vitamin K1 being added in the solution that (2) obtain, and stirs to clarify.
10. method for preparing as claimed in claim 8 is characterized in that, this method comprises:
(1) takes by weighing the water for injection of total dosing amount 50～80%, the alcoholic solution of preparation 150～200ml95%;
(2) vitamin D2 and fat-soluble antioxidant are added an amount of dissolve with ethanol, pour mixing among the Solutol Hs15 of thawing into;
(3) through ultrasonic it is melted vitamin A palmitate, again the A cetylate, vitamin E, the vitamin K1 that melt are added in the solution that (2) obtain, be stirred to into settled solution;
(4) water for injection of (1) is added in the settled solution that (3) obtain at least at twice mixing; The mode that this water for injection adds be addition from less to more, adding speed gradient type from fast to slow or gradual adding mode;
(5) in the solution that (4) obtain, add active carbon, decarburization filters then;
(6) adjust pH 6.3～6.5, again through filtering with microporous membrane, add the total dosing amount of injection water, promptly get.
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|---|---|---|---|
| CN2012102650927A CN102743394A (en) | 2012-07-30 | 2012-07-30 | Composite fat-soluable vitamin injection |
| CN2013103136969A CN103349666A (en) | 2012-07-30 | 2013-07-24 | Pharmaceutical composition injection of compound liposoluble vitamin and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2012102650927A CN102743394A (en) | 2012-07-30 | 2012-07-30 | Composite fat-soluable vitamin injection |
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| CN102743394A true CN102743394A (en) | 2012-10-24 |
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| CN2013103136969A Pending CN103349666A (en) | 2012-07-30 | 2013-07-24 | Pharmaceutical composition injection of compound liposoluble vitamin and preparation method thereof |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103349666A (en) * | 2012-07-30 | 2013-10-16 | 刘时灵 | Pharmaceutical composition injection of compound liposoluble vitamin and preparation method thereof |
| CN103462887A (en) * | 2013-08-09 | 2013-12-25 | 张蕊 | Vitamin K1 injection and preparation method thereof |
| CN104415321A (en) * | 2013-09-10 | 2015-03-18 | 成都力思特制药股份有限公司 | Cerebrolysin hydrolysate injection and preparation method thereof |
| CN105663144A (en) * | 2016-01-06 | 2016-06-15 | 施维雅(青岛)生物制药有限公司 | Fat-soluble vitamin water-based preparation for animals and preparing method and use method thereof |
| CN105663145A (en) * | 2016-01-06 | 2016-06-15 | 施维雅(青岛)生物制药有限公司 | Fat-soluble vitamin injection liquid for animals and preparing method and use method thereof |
| JP2022509196A (en) * | 2018-11-26 | 2022-01-20 | オルファニクス ゲゼルシャフト ミット ベシュレンクテル ハフツング | Aqueous pediatric retinol preparation |
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| CN112121006B (en) * | 2020-11-02 | 2021-05-11 | 苏州素仕生物科技有限公司 | Vitamin ADE composition for injection livestock and preparation method thereof |
| CN117860668B (en) * | 2023-12-06 | 2024-10-01 | 中润药业有限公司 | Vitamin K1 injection and preparation method and application thereof |
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| CN101091890A (en) * | 2007-07-26 | 2007-12-26 | 沈阳药科大学 | Composite type emulsifier, and emulsion prepared by using the emulsifier, and preparation method |
| CN102526075A (en) * | 2010-12-07 | 2012-07-04 | 西藏海思科药业集团股份有限公司 | Fat-soluble vitamin freeze-dried injection and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102743394A (en) * | 2012-07-30 | 2012-10-24 | 刘时灵 | Composite fat-soluable vitamin injection |
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- 2012-07-30 CN CN2012102650927A patent/CN102743394A/en active Pending
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| CN1843327A (en) * | 2006-04-17 | 2006-10-11 | 重庆医药工业研究院有限责任公司 | Stable freeze-dried formulation containing multiple kinds of vitamin and its preparation method |
| CN101091890A (en) * | 2007-07-26 | 2007-12-26 | 沈阳药科大学 | Composite type emulsifier, and emulsion prepared by using the emulsifier, and preparation method |
| CN102526075A (en) * | 2010-12-07 | 2012-07-04 | 西藏海思科药业集团股份有限公司 | Fat-soluble vitamin freeze-dried injection and preparation method thereof |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103349666A (en) * | 2012-07-30 | 2013-10-16 | 刘时灵 | Pharmaceutical composition injection of compound liposoluble vitamin and preparation method thereof |
| CN103462887A (en) * | 2013-08-09 | 2013-12-25 | 张蕊 | Vitamin K1 injection and preparation method thereof |
| CN104415321A (en) * | 2013-09-10 | 2015-03-18 | 成都力思特制药股份有限公司 | Cerebrolysin hydrolysate injection and preparation method thereof |
| CN105663144A (en) * | 2016-01-06 | 2016-06-15 | 施维雅(青岛)生物制药有限公司 | Fat-soluble vitamin water-based preparation for animals and preparing method and use method thereof |
| CN105663145A (en) * | 2016-01-06 | 2016-06-15 | 施维雅(青岛)生物制药有限公司 | Fat-soluble vitamin injection liquid for animals and preparing method and use method thereof |
| JP2022509196A (en) * | 2018-11-26 | 2022-01-20 | オルファニクス ゲゼルシャフト ミット ベシュレンクテル ハフツング | Aqueous pediatric retinol preparation |
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| CN103349666A (en) | 2013-10-16 |
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