CN105030662B - A kind of liposoluble vitamin D2Pharmaceutical composition and preparation method thereof - Google Patents
A kind of liposoluble vitamin D2Pharmaceutical composition and preparation method thereof Download PDFInfo
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- CN105030662B CN105030662B CN201510304605.4A CN201510304605A CN105030662B CN 105030662 B CN105030662 B CN 105030662B CN 201510304605 A CN201510304605 A CN 201510304605A CN 105030662 B CN105030662 B CN 105030662B
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Abstract
The invention discloses a kind of liposoluble vitamin D2Pharmaceutical composition and preparation method thereof, according to the ratio by 0~1g vitamin D2, 0~0.3g antioxidant, 100ml oil for injection composition.Antioxidant is added in raw material of the invention, prevents the oxidation deterioration of drug and its preparation, and by discoloration, generation precipitating and the otherwise unstability caused by aoxidizing；And the dosage of antioxidant is reasonable, the liposoluble vitamin D being prepared2Pharmaceutical composition has good stability.In addition, preparation method simple process of the invention, simple and safe operation, industrialization easy to produce.
Description
Technical field
The invention belongs to drug fields, are related to a kind of vitamin more particularly to a kind of liposoluble vitamin D2Pharmaceutical composition
Object and preparation method thereof.
Background technique
Liposoluble vitamin is as nutrient needed by human, and clinically urgent patient requires supplementation with, to maintain daily
Eubolism.Since liposoluble vitamin is not soluble in water, oral administration bioavilability is low, therefore is typically prepared into injection
Agent.
Liposoluble vitamin includes vitamin A, vitamin D2, vitamin E, vitamin K1.Vitamin D2To promote to absorb
It is required with the normal calcification institute using calcium, phosphorus and bone, adjusted together with parathyroid hormone and calcitonin serum calcium, phosphorus it is dense
Degree.Vitamin D2Calcium, phosphorus can be promoted in the absorption of small intestine, and bone can be promoted to remove calcium.
In addition to vitamin E is relatively stable, other three kinds of ingredients are unstable to light, heat and air, it is easy to degrade, therefore
There is a problem of that stability is bad in the preparation of its preparation and storage process.
Chinese patent CN102525959A, CN102357081A, CN102499939A, CN102526075A and
CN102552288A, CN101606939B, CN101940557B, CN101366712B, CN1903207A are disclosed with poly- mountain
Pear ester 80 is liposoluble vitamin solubilizer, is prepared into using mannitol as excipients freeze-dried；Chinese patent CN102429864A,
CN101129388B, CN1561970A are disclosed using soybean oil as solvent, are prepared into cream using lecithin and glycerol as cosolvent
Agent.
Chinese patent CN102247381A disclose a kind of injectable containing vitamin D2And the medicine group of vitamin E
Object and preparation method are closed, vitamin D is contained2And the pharmaceutical composition of vitamin E is made of vitamin, vitamin E, oil for injection,
Preparation is described containing vitamin D2And the processing step of the pharmaceutical composition of vitamin E, the patent do not refer to vitamin D2And dimension life
The pharmaceutical composition of plain E is more stable under which kind of ratio, does not refer to the situation of change in relation to substance also to guarantee the stabilization of drug
Property.
For uncertain factor of the existing technology, the present invention is to liposoluble vitamin D2The preparation work of pharmaceutical composition
Skill has carried out a series of researchs and has completed improvement and optimization, furtherd investigate to prescription and provide suitable pharmaceutical composition
Object is used for pharmaceutical applications.
Summary of the invention
In view of the deficiencies of the prior art, one of the objects of the present invention is to provide a kind of liposoluble vitamin D2Pharmaceutical composition
Object, stability effectively improve.
To achieve this purpose, the present invention adopts the following technical scheme:
A kind of liposoluble vitamin D2Pharmaceutical composition is made of following raw material according to the ratio:
Vitamin D20~1g, such as: 0.1g, 0.15g, 0.2g, 0.25g, 0.3g, 0.35g, 0.4g, 0.45g,
0.5g,0.55g,0.6g,0.65g,0.7g,0.75g,0.8g,0.85g,0.9g,0.95g, 1.0g；
0~0.3g of antioxidant, such as: 0.0001g, 0.0005g, 0.0009g, 0.001g, 0.005g, 0.008g,
0.01g,0.02g,0.03g,0.04g,0.05g,0.06g,0.08g,0.1g,0.15g,0.2g, 0.25g,0.3g；
Oil for injection 100ml.
Antioxidant is a kind of substance that can effectively prevent or delay autoxidation, is an important composition of excipient substance
Part, is mainly used for preventing the oxidation deterioration of drug and its preparation, and by caused by aoxidizing discoloration, generate precipitate and other
The unstability of aspect.Antioxidant itself is a kind of reducing agent, when existing simultaneously with drug, first by oxygen after antioxidant chance oxygen
Change, plays a protective role to oxidizable drug ingedient, to guarantee the stability of pharmaceutical preparation；In oxidation process, resist
The effect of oxygen agent is to provide electronics or effective hydrogen ion, and supply free radical receives, and interrupts autoxidation chain reaction.In order to guarantee to produce
The quality of product improves medicine stability, it is necessary to select suitable antioxidant.
Wherein, the antioxidant be sodium hydrogensulfite, vitamin E, vitamin C, butylated hydroxy anisole, alpha-tocopherol,
Dibutyl hydroxy toluene, sodium thiosulfate, propylgallate, ascorbyl palmitate, tert-butylhydroquinone, sulfurous acid
One of sodium, sodium pyrosulfite, dibutylphenol, thiocarbamide.
Preferably, the antioxidant is vitamin E, butylated hydroxy anisole, dibutyl hydroxy toluene, gallic acid third
One of ester, tert-butylhydroquinone.
The dosage of antioxidant of the invention is reasonable, meets the safety using amount of pharmaceutic adjuvant, can effectively improve fat-soluble dimension life
Plain D2The stability of pharmaceutical composition ensure that the safety of clinical application.
Due to liposoluble vitamin D2Not soluble in water, the present invention is using oil for injection as solvent.Wherein, the injection
Oil is one of sesame oil, corn oil, peanut oil, tea oil, soybean oil, safranine caul-fat, cotton seed oil.
Preferably, the oil for injection is one of sesame oil, peanut oil, soybean oil, cotton seed oil.
The second object of the present invention is to provide a kind of liposoluble vitamin D2The preparation method of pharmaceutical composition, including with
Lower step:
(1) raw material vitamin D is added in oil for injection heating and thermal insulation2, antioxidant, stirring keeps the temperature to being completely dissolved；
(2) active carbon is added, stirs evenly, decarburization is filtered after heat preservation；
(3) pressure filtration, then vitamin D is obtained through miillpore filter secondary filter2Admixing medical solutions；
(4) the nitrogen charging encapsulating of brown ampoule bottle is used after lamp inspection；
(5) liposoluble vitamin D is prepared after packing2Pharmaceutical composition.
Add active carbon to play decoloration, adsorb the impurity in raw material, the clarity of medical fluid can be improved.It is filled before ampoule bottle encapsulating
Nitrogen effectively prevent the oxidation deterioration of drug and its preparation, can effectively improve the stability of drug.
Wherein, further include following steps before step (1): processing district, equipment, ingredient utensil, potting fixture are sterilized；Step
Suddenly the holding temperature in (1) is 40~60 DEG C, such as 40 DEG C, 45 DEG C, 50 DEG C, 55 DEG C, 60 DEG C；Soaking time in step (2)
For 0.5h~2h, such as 0.5h, 1h, 1.5h, 2h；Miillpore filter in step (3) having a size of 0.22 μm~0.8 μm, such as
0.22μm、0.25μm、0.3μm、0.35μm、 0.4μm、0.45μm、0.5μm、0.55μm、0.6μm、0.65μm、0.7μm、0.75
μm、0.8μm。
Wherein, the sterilisation temp is 110~130 DEG C, and the time of the disinfection is 10~30min；After step (4)
Further include the steps that moist heat sterilization, leak detection, the moist heat sterilization temperature be 110~130 DEG C, the moist heat sterilization time be 10~
30min。
Compared with prior art, the invention has the benefit that a kind of liposoluble vitamin D2Pharmaceutical composition and its system
Preparation Method, according to the ratio by 0~1g vitamin D2, 0~0.3g antioxidant, 100ml oil for injection composition.Add in raw material of the invention
Enter antioxidant, prevents the oxidation deterioration of drug and its preparation, and by discoloration, generation precipitating and other aspects caused by aoxidizing
Unstability；And the dosage of antioxidant is reasonable, ensure that the safety of clinical application, liposoluble vitamin D of the invention2
Pharmaceutical composition has good stability.
Liposoluble vitamin D of the invention2Antioxidant is added in pharmaceutical composition, and nitrogen filled protection in preparation process makes to prepare
Liposoluble vitamin D2Pharmaceutical composition stability improves, and simplifies preparation process, and simple and safe operation is easy to produce
Industrialization.
Specific embodiment
The technical scheme of the invention is further explained by means of specific implementation.
Unless specific instructions, various raw materials of the invention are commercially available buys, or is prepared according to the conventional method of this field
It obtains.
Impurity refers to the stability and curative effect present in drug without therapeutic effect or influence drug, or even has to people's health
Harmful substance.The source of impurity, it is main there are two: first is that by being introduced in production process；Second is that by extraneous item in storage
The influence of part causes drug physics and chemistry to be held and changes and generate.Due to some in raw materials used impure or raw materials used
Unreacted is complete and the presence of reaction intermediate and byproduct of reaction, fails to completely remove in purification, can all make product
In there are impurity.In storage under the influence of the external conditions such as temperature, humidity, daylight, air, or because of the work of microorganism
With, cause drug occur hydrolysis, oxidation, decomposition, isomerization, crystal transfer, polymerization, deliquescence and it is mouldy etc. change, make in drug
Generate related impurity.The appearance character of drug is not only set to change, it is often more important that reduce the stability and matter of drug
Amount, or even lose curative effect or murder by poisoning is generated to human body.In order to detect medicine stability, common influence factor experiment includes high temperature
Test, high humidity experiment and exposure experiments to light.The general temperature of hot test is higher than 10 DEG C of accelerated test temperature or more (such as 50 DEG C, 60 DEG C
Deng), high humidity test generallys use relative humidity 75% or higher (such as 92.5%RH), and the total illumination of exposure experiments to light is not less than
1.2×106Luxhr, near ultraviolet energy are not less than 200whr/m2。
Liposoluble vitamin D of the invention2Pharmaceutical composition detection method of content refers to vitamin D2Raw material detection method,
Reaching formulation content limit is 95%~105%, meets pharmacopeia and requires accordingly, meanwhile, the present invention refers to Chinese Pharmacopoeia annex
Liposoluble vitamin D of the sterile and Test for Bacterial Endotoxins to preparation in method2Pharmaceutical composition is detected, detection
As a result qualified.
The fat-soluble dimension that the present invention passes through hot test and exposure experiments to light relatively this experiment preparation in influence factor test
Raw element D2The impurity content of pharmaceutical composition and reference reagent investigates the liposoluble vitamin D of this experiment preparation with this2Drug
The product quality and stability of composition.Reference reagent of the invention is the vitamin D of certain factory production2Injection, institute of the present invention
It is as shown in table 1 with equipment.
Table 1
| Instrument and equipment | Model | Producer |
| High performance liquid chromatograph | Waters e2695/2489 | Water generation Science and Technology Ltd. |
| Gas chromatograph | GC-2010 PLUS | Shimadzu gas phase Co., Ltd |
| Electronic balance | XS1505 | METTLER TOLEDO |
| PH meter | Sevevn Easy | METTLER TOLEDO |
| Baking oven | FED240 | BINDER |
| Lighting box | LS-4000/UV | Beijing TianXing tech |
| Chromatographic column | 5 μm, 4.6*250mm | THERMO |
Comparative example
Quantitative analysis, available reference reagent are carried out to reference reagent using high performance liquid chromatograph, gas chromatograph
Contain following component:
Vitamin D20.5g；
Vitamin E 0.0076g；
Soybean oil 100ml.
Its impurity content will be surveyed respectively after reference reagent high temperature 10 days, illumination 12 days, experimental result is shown in Table shown in 2.
Embodiment 1
The liposoluble vitamin D of the present embodiment2Pharmaceutical composition configures to obtain using prescription identical with comparative example, by following
The material of proportion forms:
Vitamin D20.5g；
Vitamin E 0.0076g；
Soybean oil 100ml.
The preparation method is as follows:
(1) processing district, equipment, ingredient utensil, potting fixture disinfection are spare, and 121 DEG C, 30min disinfection is spare；
(2) raw material vitamin D is added to 60 DEG C in injection soybean oil heating and thermal insulation2, vitamin E, stirring to completely it is molten
Solution, heat preservation；
(3) active carbon is added, stirs evenly, filters decarburization after keeping the temperature 2h；
(4) pressure filtration, then vitamin D is obtained through 0.45 μm of miillpore filter secondary filter2Admixing medical solutions；
(5) encapsulating advance portable lighter is examined, and uses the nitrogen charging encapsulating of brown ampoule bottle after qualified；
(6) 121 DEG C, 30min moist heat sterilization is hunted leak, lamp inspection, and liposoluble vitamin D is prepared in packaging2Pharmaceutical composition
Object.
The liposoluble vitamin D that will be prepared2Pharmaceutical composition high temperature is surveyed its impurity after 10 days, illumination 12 days respectively and is contained
Amount, experimental result are shown in Table shown in 2.
Embodiment 2
The liposoluble vitamin D of the present embodiment2Pharmaceutical composition is made of the material of following proportions:
Vitamin D20.5g；
Vitamin E 0.1g；
Soybean oil 100ml.
The preparation method is as follows:
(1) processing district, equipment, ingredient utensil, potting fixture disinfection are spare, and 121 DEG C, 30min disinfection is spare；
(2) raw material vitamin D is added to 50 DEG C in injection soybean oil heating and thermal insulation2, vitamin E, stirring to completely it is molten
Solution, heat preservation；
(3) active carbon is added, stirs evenly, filters decarburization after keeping the temperature 2h；
(4) pressure filtration, then vitamin D is obtained through 0.45 μm of miillpore filter secondary filter2Admixing medical solutions；
(5) encapsulating advance portable lighter is examined, and uses the nitrogen charging encapsulating of brown ampoule bottle after qualified；
(6) 121 DEG C, 30min moist heat sterilization is hunted leak, lamp inspection, and liposoluble vitamin D is prepared in packaging2Pharmaceutical composition
Object.
The liposoluble vitamin D that will be prepared2Pharmaceutical composition high temperature is surveyed its impurity after 10 days, illumination 12 days respectively and is contained
Amount, experimental result are shown in Table shown in 2.
Embodiment 3
The liposoluble vitamin D of the present embodiment2Pharmaceutical composition is made of the material of following proportions:
Vitamin D21g；
Butylated hydroxy anisole 0.05g；
Peanut oil 100ml.
The preparation method is as follows:
(1) processing district, equipment, ingredient utensil, potting fixture disinfection are spare, and 125 DEG C, 20min disinfection is spare；
(2) raw material vitamin D is added to 50 DEG C in injection peanut oil heating and thermal insulation2, butylated hydroxy anisole, stirring extremely
It is completely dissolved, keeps the temperature；
(3) active carbon is added, stirs evenly, filters decarburization after keeping the temperature 1h；
(4) pressure filtration, then vitamin D is obtained through 0.22 μm of miillpore filter secondary filter2Admixing medical solutions；
(5) encapsulating advance portable lighter is examined, and uses the nitrogen charging encapsulating of brown ampoule bottle after qualified；
(6) 125 DEG C, 20min moist heat sterilization is hunted leak, lamp inspection, and liposoluble vitamin D is prepared in packaging2Pharmaceutical composition
Object.
The liposoluble vitamin D that will be prepared2Pharmaceutical composition high temperature is surveyed its impurity after 10 days, illumination 12 days respectively and is contained
Amount, experimental result are shown in Table shown in 2.
Embodiment 4
The liposoluble vitamin D of the present embodiment2Pharmaceutical composition is made of the material of following proportions:
Vitamin D20.8g；
Dibutyl hydroxy toluene 0.3g；
Sesame oil 100ml.
The preparation method is as follows:
(1) processing district, equipment, ingredient utensil, potting fixture disinfection are spare, and 130 DEG C, 10min disinfection is spare；
(2) raw material vitamin D is added to 40 DEG C in injection sesame oil heating and thermal insulation2, dibutyl hydroxy toluene, stirring extremely
It is completely dissolved, keeps the temperature；
(3) active carbon is added, stirs evenly, filters decarburization after keeping the temperature 1.5h；
(4) pressure filtration, then vitamin D is obtained through 0.8 μm of miillpore filter secondary filter2Admixing medical solutions；
(5) encapsulating advance portable lighter is examined, and uses the nitrogen charging encapsulating of brown ampoule bottle after qualified；
(6) 130 DEG C, 10min moist heat sterilization is hunted leak, lamp inspection, and liposoluble vitamin D is prepared in packaging2Pharmaceutical composition
Object.
The liposoluble vitamin D that will be prepared2Pharmaceutical composition high temperature is surveyed its impurity after 10 days, illumination 12 days respectively and is contained
Amount, experimental result are shown in Table shown in 2.
Embodiment 5
The liposoluble vitamin D of the present embodiment2Pharmaceutical composition is made of the material of following proportions:
Vitamin D20.2g；
Propylgallate 0.2g；
Cotton seed oil 100ml.
The preparation method is as follows:
(1) processing district, equipment, ingredient utensil, potting fixture disinfection are spare, and 110 DEG C, 25min disinfection is spare；
(2) raw material vitamin D is added to 55 DEG C in injection cotton seed oil heating and thermal insulation2, propylgallate, stirring is to complete
Fully dissolved, heat preservation；
(3) active carbon is added, stirs evenly, filters decarburization after keeping the temperature 0.5h；
(4) pressure filtration, then vitamin D is obtained through 0.45 μm of miillpore filter secondary filter2Admixing medical solutions；
(5) encapsulating advance portable lighter is examined, and uses the nitrogen charging encapsulating of brown ampoule bottle after qualified；
(6) 130 DEG C, 10min moist heat sterilization is hunted leak, lamp inspection, and liposoluble vitamin D is prepared in packaging2Pharmaceutical composition
Object.
The liposoluble vitamin D that will be prepared2Pharmaceutical composition high temperature is surveyed its impurity after 10 days, illumination 12 days respectively and is contained
Amount, experimental result are shown in Table shown in 2.
Embodiment 6
The liposoluble vitamin D of the present embodiment2Pharmaceutical composition is made of the material of following proportions:
Vitamin D20.1g；
Tert-butylhydroquinone 0.1g；
Soybean oil 100ml.
The preparation method is as follows:
(1) processing district, equipment, ingredient utensil, potting fixture disinfection are spare, and 121 DEG C, 30min disinfection is spare；
(2) raw material vitamin D is added to 50 DEG C in injection soybean oil heating and thermal insulation2, tert-butylhydroquinone, stirring extremely
It is completely dissolved, keeps the temperature；
(3) active carbon is added, stirs evenly, filters decarburization after keeping the temperature 2h；
(4) pressure filtration, then vitamin D is obtained through 0.45 μm of miillpore filter secondary filter2Admixing medical solutions；
(5) encapsulating advance portable lighter is examined, and uses the nitrogen charging encapsulating of brown ampoule bottle after qualified；
(6) 121 DEG C, 30min moist heat sterilization is hunted leak, lamp inspection, and liposoluble vitamin D is prepared in packaging2Pharmaceutical composition
Object.
The liposoluble vitamin D that will be prepared2Pharmaceutical composition high temperature is surveyed its impurity after 10 days, illumination 12 days respectively and is contained
Amount, experimental result are shown in Table shown in 2.
Embodiment 7
The liposoluble vitamin D of the present embodiment2Pharmaceutical composition is made of the material of following proportions:
Vitamin D20.5g；
Butylated hydroxy anisole 0.1g；
Soybean oil 100ml.
The preparation method is as follows:
(1) processing district, equipment, ingredient utensil, potting fixture disinfection are spare, and 110 DEG C, 30min disinfection is spare；
(2) raw material vitamin D is added to 55 DEG C in injection soybean oil heating and thermal insulation2, butylated hydroxy anisole, stirring extremely
It is completely dissolved, keeps the temperature；
(3) active carbon is added, stirs evenly, filters decarburization after keeping the temperature 2h；
(4) pressure filtration, then vitamin D is obtained through 0.45 μm of miillpore filter secondary filter2Admixing medical solutions；
(5) encapsulating advance portable lighter is examined, and uses the nitrogen charging encapsulating of brown ampoule bottle after qualified；
(6) 121 DEG C, 20min moist heat sterilization is hunted leak, lamp inspection, and liposoluble vitamin D is prepared in packaging2Pharmaceutical composition
Object.
The liposoluble vitamin D that will be prepared2Pharmaceutical composition high temperature is surveyed its impurity after 10 days, illumination 12 days respectively and is contained
Amount, experimental result are shown in Table shown in 2.
Embodiment 8
The liposoluble vitamin D of the present embodiment2Pharmaceutical composition is made of the material of following proportions:
Vitamin D20.5g；
Butylated hydroxy anisole 0g；
Soybean oil 100ml.
The preparation method is as follows:
(1) processing district, equipment, ingredient utensil, potting fixture disinfection are spare, and 115 DEG C, 30min disinfection is spare；
(2) raw material vitamin D is added to 60 DEG C in injection soybean oil heating and thermal insulation2, butylated hydroxy anisole, stirring extremely
It is completely dissolved, keeps the temperature；
(3) active carbon is added, stirs evenly, filters decarburization after keeping the temperature 0.5h；
(4) pressure filtration, then vitamin D is obtained through 0.22 μm of miillpore filter secondary filter2Admixing medical solutions；
(5) encapsulating advance portable lighter is examined, and uses the nitrogen charging encapsulating of brown ampoule bottle after qualified；
(6) 115 DEG C, 30min moist heat sterilization is hunted leak, lamp inspection, and liposoluble vitamin D is prepared in packaging2Pharmaceutical composition
Object.
The liposoluble vitamin D that will be prepared2Pharmaceutical composition high temperature is surveyed its impurity after 10 days, illumination 12 days respectively and is contained
Amount, experimental result are shown in Table shown in 2.
Embodiment 9
The liposoluble vitamin D of the present embodiment2Pharmaceutical composition is made of the material of following proportions:
Vitamin D20.5g；
Vitamin E 0.01g；
Sesame oil 100ml.
The preparation method is as follows:
(1) processing district, equipment, ingredient utensil, potting fixture disinfection are spare, and 121 DEG C, 15min disinfection is spare；
(2) raw material vitamin D is added to 50 DEG C in injection sesame oil heating and thermal insulation2, vitamin E, stirring to completely it is molten
Solution, heat preservation；
(3) active carbon is added, stirs evenly, filters decarburization after keeping the temperature 1.5h；
(4) pressure filtration, then vitamin D is obtained through 0.45 μm of miillpore filter secondary filter2Admixing medical solutions；
(5) encapsulating advance portable lighter is examined, and uses the nitrogen charging encapsulating of brown ampoule bottle after qualified；
(6) 121 DEG C, 15min moist heat sterilization is hunted leak, lamp inspection, and liposoluble vitamin D is prepared in packaging2Pharmaceutical composition
Object.
The liposoluble vitamin D that will be prepared2Pharmaceutical composition high temperature is surveyed its impurity after 10 days, illumination 12 days respectively and is contained
Amount, experimental result are shown in Table shown in 2.
Embodiment 10
The liposoluble vitamin D of the present embodiment2Pharmaceutical composition is made of the material of following proportions:
Vitamin D20.5g；
Dibutyl hydroxy toluene 0.04g；
Sesame oil 100ml.
The preparation method is as follows:
(1) processing district, equipment, ingredient utensil, potting fixture disinfection are spare, and 121 DEG C, 20min disinfection is spare；
(2) raw material vitamin D is added to 50 DEG C in injection sesame oil heating and thermal insulation2, dibutyl hydroxy toluene, stirring extremely
It is completely dissolved, keeps the temperature；
(3) active carbon is added, stirs evenly, filters decarburization after keeping the temperature 2h；
(4) pressure filtration, then vitamin D is obtained through 0.45 μm of miillpore filter secondary filter2Admixing medical solutions；
(5) encapsulating advance portable lighter is examined, and uses the nitrogen charging encapsulating of brown ampoule bottle after qualified；
(6) 121 DEG C, 30min moist heat sterilization is hunted leak, lamp inspection, and liposoluble vitamin D is prepared in packaging2Pharmaceutical composition
Object.
The liposoluble vitamin D that will be prepared2Pharmaceutical composition high temperature is surveyed its impurity after 10 days, illumination 12 days respectively and is contained
Amount, experimental result are shown in Table shown in 2.
Embodiment 11
The liposoluble vitamin D of the present embodiment2Pharmaceutical composition is made of the material of following proportions:
Vitamin D20.5g；
Propylgallate 0.06g；
Soybean oil 100ml.
The preparation method is as follows:
(1) processing district, equipment, ingredient utensil, potting fixture disinfection are spare, and 115 DEG C, 30min disinfection is spare；
(2) raw material vitamin D is added to 55 DEG C in injection soybean oil heating and thermal insulation2, propylgallate, stirring is to complete
Fully dissolved, heat preservation；
(3) active carbon is added, stirs evenly, filters decarburization after keeping the temperature 2h；
(4) pressure filtration, then vitamin D is obtained through 0.45 μm of miillpore filter secondary filter2Admixing medical solutions；
(5) encapsulating advance portable lighter is examined, and uses the nitrogen charging encapsulating of brown ampoule bottle after qualified；
(6) 121 DEG C, 20min moist heat sterilization is hunted leak, lamp inspection, and liposoluble vitamin D is prepared in packaging2Pharmaceutical composition
Object.
The liposoluble vitamin D that will be prepared2Pharmaceutical composition high temperature is surveyed its impurity after 10 days, illumination 12 days respectively and is contained
Amount, experimental result are shown in Table shown in 2.
Embodiment 12
The liposoluble vitamin D of the present embodiment2Pharmaceutical composition is made of the material of following proportions:
Vitamin D20.5g；
Vitamin E 0.08g；
Soybean oil 100ml.
The preparation method is as follows:
(1) processing district, equipment, ingredient utensil, potting fixture disinfection are spare, and 130 DEG C, 30min disinfection is spare；
(2) raw material vitamin D is added to 55 DEG C in injection sesame oil heating and thermal insulation2, vitamin E, stirring to completely it is molten
Solution, heat preservation；
(3) active carbon is added, stirs evenly, filters decarburization after keeping the temperature 2h；
(4) pressure filtration, then vitamin D is obtained through 0.45 μm of miillpore filter secondary filter2Admixing medical solutions；
(5) encapsulating advance portable lighter is examined, and uses the nitrogen charging encapsulating of brown ampoule bottle after qualified；
(6) 121 DEG C, 20min moist heat sterilization is hunted leak, lamp inspection, and liposoluble vitamin D is prepared in packaging2Pharmaceutical composition
Object.
Embodiment 13
The liposoluble vitamin D of the present embodiment2Pharmaceutical composition is made of the material of following proportions:
Vitamin D20.5g；
Vitamin E 0.03g；
Soybean oil 100ml.
The preparation method is as follows:
(1) processing district, equipment, ingredient utensil, potting fixture disinfection are spare, and 130 DEG C, 30min disinfection is spare；
(2) raw material vitamin D is added to 60 DEG C in injection soybean oil heating and thermal insulation2, vitamin E, stirring to completely it is molten
Solution, heat preservation；
(3) active carbon is added, stirs evenly, filters decarburization after keeping the temperature 2h；
(4) pressure filtration, then vitamin D is obtained through 0.8 μm of miillpore filter secondary filter2Admixing medical solutions；
(5) encapsulating advance portable lighter is examined, and uses the nitrogen charging encapsulating of brown ampoule bottle after qualified；
(6) 130 DEG C, 30min moist heat sterilization is hunted leak, lamp inspection, and liposoluble vitamin D is prepared in packaging2Pharmaceutical composition
Object.
Embodiment 14
The liposoluble vitamin D of the present embodiment2Pharmaceutical composition is made of the material of following proportions:
Vitamin D20.5g；
Vitamin E 0.0001g；
Soybean oil 100ml.
The preparation method is as follows:
(1) processing district, equipment, ingredient utensil, potting fixture disinfection are spare, and 110 DEG C, 10min disinfection is spare；
(2) raw material vitamin D is added to 40 DEG C in injection soybean oil heating and thermal insulation2, vitamin E, stirring to completely it is molten
Solution, heat preservation；
(3) active carbon is added, stirs evenly, filters decarburization after keeping the temperature 0.5h；
(4) pressure filtration, then vitamin D is obtained through 0.22 μm of miillpore filter secondary filter2Admixing medical solutions；
(5) encapsulating advance portable lighter is examined, and uses the nitrogen charging encapsulating of brown ampoule bottle after qualified；
(6) 110 DEG C, 10min moist heat sterilization is hunted leak, lamp inspection, and liposoluble vitamin D is prepared in packaging2Pharmaceutical composition
Object.
Embodiment 15
The liposoluble vitamin D of the present embodiment2Pharmaceutical composition is made of the material of following proportions:
Vitamin D20.5g；
Butylated hydroxy anisole 0.15g；
Soybean oil 100ml.
The preparation method is as follows:
(1) processing district, equipment, ingredient utensil, potting fixture disinfection are spare, and 120 DEG C, 20min disinfection is spare；
(2) raw material vitamin D is added to 50 DEG C in injection soybean oil heating and thermal insulation2, butylated hydroxy anisole, stirring extremely
It is completely dissolved, keeps the temperature；
(3) active carbon is added, stirs evenly, filters decarburization after keeping the temperature 1.5h；
(4) pressure filtration, then vitamin D is obtained through 0.45 μm of miillpore filter secondary filter2Admixing medical solutions；
(5) encapsulating advance portable lighter is examined, and uses the nitrogen charging encapsulating of brown ampoule bottle after qualified；
(6) 120 DEG C, 20min moist heat sterilization is hunted leak, lamp inspection, and liposoluble vitamin D is prepared in packaging2Pharmaceutical composition
Object.
Embodiment 16
The liposoluble vitamin D of the present embodiment2Pharmaceutical composition is made of the material of following proportions:
Vitamin D20.5g；
Propylgallate 0.12g；
Soybean oil 100ml.
The preparation method is as follows:
(1) processing district, equipment, ingredient utensil, potting fixture disinfection are spare, and 121 DEG C, 25min disinfection is spare；
(2) raw material vitamin D is added to 55 DEG C in injection soybean oil heating and thermal insulation2, propylgallate, stirring is to complete
Fully dissolved, heat preservation；
(3) active carbon is added, stirs evenly, filters decarburization after keeping the temperature 2h；
(4) pressure filtration, then vitamin D is obtained through 0.45 μm of miillpore filter secondary filter2Admixing medical solutions；
(5) encapsulating advance portable lighter is examined, and uses the nitrogen charging encapsulating of brown ampoule bottle after qualified；
(6) 121 DEG C, 25min moist heat sterilization is hunted leak, lamp inspection, and liposoluble vitamin D is prepared in packaging2Pharmaceutical composition
Object.
The liposoluble vitamin D that will be prepared2Pharmaceutical composition first carries out content, sterile and detection of bacterial endotoxin,
After all indexs meet regulation, its impurity content is surveyed respectively after placing high temperature 10 days, illumination 12 days, experimental result is shown in Table 2 institutes
Show.
Table 2
It can be seen from 2 testing result of table after high temperature 10 days, illumination 12 days, liposoluble vitamin prepared by the present invention
D2The largest single impurity of pharmaceutical composition and total miscellaneous all smaller than the reference reagent in comparative example, illustrates fat-soluble dimension of the invention
Raw element D2The stability of pharmaceutical composition is more preferable, keeps clinical application safer；By comparative example and embodiment 1, same materials are used
The liposoluble vitamin D of method preparation of the invention2Pharmaceutical composition stability is more preferable.Preparation method technique letter of the invention
It is single, industrialization easy to produce.
Above embodiments are only used to illustrate method detailed of the invention, and the invention is not limited to above-mentioned method detaileds, i.e.,
Do not mean that the invention must rely on the above detailed methods to implement.It should be clear to those skilled in the art, right
Any improvement of the invention, the addition of equivalence replacement and auxiliary element to each raw material of product of the present invention, the selection of concrete mode
Deng all of which fall within the scope of protection and disclosure of the present invention.
Claims (8)
1. a kind of liposoluble vitamin D2The preparation method of pharmaceutical composition, which comprises the following steps:
(1) raw material vitamin D is added in oil for injection heating and thermal insulation2, stirring is to being completely dissolved, and heat preservation, wherein holding temperature is 40
~60 DEG C；
(2) active carbon is added, stirs evenly, decarburization is filtered after heat preservation, wherein soaking time is 0.5h~2h；
(3) pressure filtration, then vitamin D is obtained through miillpore filter secondary filter2Admixing medical solutions, wherein miillpore filter having a size of
0.22~0.8 μm；
(4) the nitrogen charging encapsulating of brown ampoule bottle is used after lamp inspection；
(5) liposoluble vitamin D is prepared after packing2Pharmaceutical composition；
The wherein liposoluble vitamin D2It is made of following raw material according to the ratio: vitamin D20.1~1.0g and oil for injection
100ml；
The oil for injection is one of sesame oil, corn oil, peanut oil, tea oil, soybean oil, safranine caul-fat, cotton seed oil.
2. a kind of liposoluble vitamin D according to claim 12The preparation method of pharmaceutical composition, which is characterized in that institute
Further include following steps before stating step (1): processing district, equipment, ingredient utensil, potting fixture being sterilized, the sterilisation temp
It is 110~130 DEG C, the time of the disinfection is 10~30min.
3. a kind of liposoluble vitamin D according to claim 12The preparation method of pharmaceutical composition, which is characterized in that institute
It states step (4) and further includes the steps that moist heat sterilization, leak detection later, the moist heat sterilization temperature is 110~130 DEG C, described damp and hot
Sterilization time is 10~30min.
4. preparation method described in any claim prepares resulting liposoluble vitamin D in a kind of claims 1 to 32Medicine group
Close object, which is characterized in that be made of following raw material according to the ratio:
Vitamin D20.1~1.0g；
Oil for injection 100ml.
5. liposoluble vitamin D according to claim 42Pharmaceutical composition, which is characterized in that according to the ratio by following raw material
Composition:
Vitamin D20.1~0.5g；
Oil for injection 100ml.
6. liposoluble vitamin D according to claim 52Pharmaceutical composition, which is characterized in that according to the ratio by following raw material
Composition:
Vitamin D20.5g；
Oil for injection 100ml.
7. liposoluble vitamin D according to claim 62Pharmaceutical composition, which is characterized in that the oil for injection is sesame
One of sesame oil, corn oil, peanut oil, tea oil, soybean oil, safranine caul-fat, cotton seed oil.
8. liposoluble vitamin D according to claim 72Pharmaceutical composition, which is characterized in that the oil for injection is sesame
One of sesame oil, peanut oil, soybean oil, cotton seed oil.
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| CN103191134B (en) * | 2013-04-26 | 2014-02-12 | 四川省惠达药业有限公司 | Pharmaceutical composition of lipid-soluble vitamin and preparation method thereof |
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