CN106890338A - A kind of vitamin D class preparation containing squalene plant oil - Google Patents
A kind of vitamin D class preparation containing squalene plant oil Download PDFInfo
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- CN106890338A CN106890338A CN201710103776.XA CN201710103776A CN106890338A CN 106890338 A CN106890338 A CN 106890338A CN 201710103776 A CN201710103776 A CN 201710103776A CN 106890338 A CN106890338 A CN 106890338A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/07—Retinol compounds, e.g. vitamin A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/592—9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
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Abstract
The invention belongs to field of pharmaceutical preparations, more particularly to a kind of vitamin D class preparation containing squalene plant oil.The preparation is will to be sufficiently stirred for containing squalene plant oil and vitamin D active component, mix it, be made liquid, liquid then is made into soft capsule, capsule-type drops and drops.The vegetable oil containing squalene in compound preparation of the invention can not only protect the stability of vitamin D class preparation, also with antitumor, anti-oxidant, antifatigue, anti-infective and strengthen immunity effect.The preparation method process is simple of invention, stabilization, favorable reproducibility, while ensure that vitamin vitamin D class preparation curative effect, improve the quality of the life of children, ensure the physical and mental health of children.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, it is related to a kind of vitamin D class preparation containing squalene plant oil.
Technical background
Squalene also known as MF59, squalene, Squalene, entitled 2,6,10,15,19,23- hexamethyl -2 of chemistry,
The alkene of 6,10,14,18,22- tetracosa carbon six, is a kind of height unsaturation hydrocarbon compound, initially by Japanese chemists in 1906
Year finds in black dogfish oil.Squalene is a kind of natural triterpene alkenes, polyunsaturated fat race hydrocarbon compound, squalene
Essentially from eepwater shark liver oil, lipid content more than 90% is accounted for, while be also present in crude vegetal, especially in olive
Oil, palm oil content are more；The vegetable oil such as rapeseed oil, soybean oil, peanut oil, cottonseed oil also contain a certain amount of squalene, but contain
Amount is less.
The average content mg/100g of squalene in the Vegetable Oils of table 1
Although there is document report squalene there is antitumor, anti-oxidant, radioresistance, removing toxic substances and strengthen immunity etc. to make
With.But there is squalene the aspects such as the stability for improving vitamin D class preparation to have no document report.This patent passes through many experiments
Research shows：Vegetable oil vitamin D class preparation containing squalene can significantly improve the stability of vitamin D class preparation, this steady
Qualitatively improve relevant in the content of vegetable oil with squalene, when content of the squalene in vegetable oil is 52~506mg/100g
When, squalene content is higher, and vitamin D class preparation stability is better.In addition study and also show squalene containing in vegetable oil
Measure during for 52~458mg/100g, with anti-infective, anti-oxidant and fatigue-resisting function；During less than 52mg/100g, or it is higher than
During 458mg/100g, above-mentioned effect not substantially, it is optimal be squalene in crude vegetal content be 206~395mg/
The vitamin D class preparation of 100g；Natural plants containing the vitamin D class preparation in squalene plant oil than exogenous addition squalene
Above-mentioned effect of vitamin D class preparation in thing oil more preferably can also avoid the side effects such as diarrhoea.
Vitamin D is the necessary material of growth in humans's development, especially to development of fetus, epithelial tissue constancy, eyesight, reproduction
Function, bone growth and blood calcium regulation etc. play an important role.Be deficient in vitamin D, and immunologic function can be than relatively low, upper respiratory tract appearance
It is subject to the infringement of bacterium and virus.
Presently commercially available vitamin D class preparation nearly all contains vegetable oil, and vegetable oil is almost soybean oil and peanut
Oil, the exogenous grease that the vegetable oil in vitamin D class preparation is mainly taken in for infant, therefore produce containing squalene plant
The vitamin D class preparation of oil, the quality of the life for improving infant is very important.
On the basis of the present invention is also based on ensureing that infant is physically and mentally healthy, carried out using oil containing squalene plant a series of
Produced on the basis of research and practice.
The content of the invention
It is an object of the invention to provide a kind of vitamin D class preparation containing squalene plant oil, one kind has guarantee baby
The physically and mentally healthy and convenient to take compound preparation of child.
In order to reach time purpose, the present invention uses following technical scheme：
A kind of vitamin D class preparation containing squalene plant oil, it is characterised in that the oil containing squalene plant includes day
It is right, semi-synthetic or artificial modification containing squalene plant oil.
Further, described a kind of vitamin D class preparation containing squalene plant oil, it is characterised in that described containing spiny dogfish
Squalene content should be 52mg~506mg/100g in alkene vegetable oil.
Further, described a kind of vitamin D class preparation containing squalene plant oil, it is characterised in that described containing spiny dogfish
Squalene content should be 206mg~458mg/100g in alkene vegetable oil.
Further, described a kind of vitamin D class preparation containing squalene plant oil, it is characterised in that described containing spiny dogfish
Squalene content is defined as 206mg~395mg/100g in alkene vegetable oil.
Further, described a kind of vitamin D class preparation containing squalene plant oil, it is characterised in that described containing angle
MF59 vegetable oil is natural containing squalene plant oil.
Further, described a kind of vitamin D class preparation containing squalene plant oil, it is characterised in that described natural
The oil containing squalene plant is the mixing of one or more in olive oil, palm oil, rice bran oil and amaranth rapeseed oil.
Further, described a kind of vitamin D class preparation containing squalene plant oil, it is characterised in that described natural
Containing squalene plant oil be olive oil.
Further, a kind of described vitamin D class preparation containing squalene plant oil, it is characterised in that the vitamin D
Class preparation includes vitamin D single preparations of ephedrine and vitaminAD compound preparation.
Further, a kind of described vitamin D class preparation containing squalene plant oil, it is characterised in that the vitamin D
Single preparations of ephedrine is vitamin D2Or D3。
Further, a kind of described vitamin D class preparation containing squalene plant oil, it is characterised in that the vitamin
AD compound preparations are that vitamin A and vitamin D are prepared into the vitamin D class preparation containing squalene plant oil by a certain percentage.
Further, a kind of described vitamin D class preparation containing squalene plant oil, it is characterised in that the vitamin
Vitamin A is A in AD compound preparations1, the vitamin D is D2Or D3。
Further, a kind of described vitamin D class preparation containing squalene plant oil, it is characterised in that the vitamin A
It is 0.5~10 with the I.U. ratios of vitamin D:1.
Further, a kind of described vitamin D class preparation containing squalene plant oil, it is characterised in that the dimension life
The I.U. ratios of plain A and vitamin D are 10:1、20:7 and 3:1.
A kind of vitamin D class preparation containing squalene plant oil of the present invention, the preparation is soft capsule, capsule-type
Drops and drops.
Further, a kind of vitamin D class preparation containing squalene plant oil stated, it is characterised in that the preparation is
VitaminAD containing olive oil2Or vitaminAD3Capsule-type drops.
Further, described a kind of vitamin D class preparation containing squalene plant oil, it is characterised in that the preparation is
Vitamin D containing olive oil2Or vitamin D3Capsule-type drops.
Further, described a kind of vitamin D class preparation containing squalene plant oil, the preparation method is：In heating
Under the conditions of, vitamin D class agent activity composition is added to makes it fully mix containing heating stirring in squalene plant oil, that is, contain
Squalene plant oil is heated jointly with active component, and can carry out lasting mixing to material by external force in heating process, it is ensured that
Material dispersion is uniform, by thermal balance.Colloidal film is crossed when temperature is down to 25 DEG C, content is made.
Further, described content is further prepared into the dimension containing squalene plant oil by automatic rotary transformation of ownership capsule machine pressure
Raw element D class preparations.
The implementation of preparation method of the invention does not need special installation, and required equipment possesses heating and agitating function, pair plus
Heat and the no particular/special requirement of mixing, purpose is only as far as possible to be heated evenly mixed material each several part, internal batch temperature equilibrium,
Mix between each composition of material and be uniformly dispersed.
The present invention also protects the compound preparation obtained by the preparation method of any one of the present invention.
Beneficial effects of the present invention：
The preparation method is that the vegetable oil in prescription is defined as to contain containing squalene plant oil, and regulation squalene
It is 206mg~395mg/100g to measure, and provide not only the stability of vitamin D class preparation, improves the quality of the life of children, is ensured
Infant is physically and mentally healthy.And preparation process is simple, technique favorable reproducibility.
The implementation of preparation method of the present invention does not need special installation, and required equipment possesses heating and agitating function,
To heating and mixing no particular/special requirement, purpose is only as far as possible to be heated evenly mixed material each several part, internal batch temperature
Mix between balanced, each composition of material and be uniformly dispersed.Compared with other method, biggest advantage can be just to use common production
Equipment carries out the production of preparation, and need not increase extra operation, equipment investment is so reduced to greatest extent, and simplify work
The production operation of people, shortens the production cycle, while product quality is ensured, farthest reduces being produced into for product
This, is conducive to industrialization to mass produce.
Specific embodiment
In order that the object, technical solutions and advantages of the present invention are clearer, the preferred embodiments of the present invention are entered below
The detailed description of row, and carry out related experiment.Using document《The measure of squalene content in camellia seed oil》(author：Zhang Dongsheng,
Xue Yalin, Jin Qingzhe, wait to originate：《Chinese oil》Magazine, 11 phases in 2013, the page number：85-88) the gas chromatography pair for providing
Squalene in each embodiment vegetable oil carries out assay.
The vitamin A ＆ D capsule type drops of embodiment 1
1st, prescription：Every contains the unit of retinol1 500 and vitamin D2500 units
2nd, capsule prescription
3rd, preparation method
3.1 dispensings
3.1.1 weigh
The bucket heating water bath of vitamin A will be contained, control 57~60 DEG C of bath temperature, until oleovitamin A clarification nothing
It can be seen that standby (vitamin A feeds intake by 110%) is weighed after crystallization again.Other supplementary material (vitamin Ds are weighed by recipe quantity2Press
107% feeds intake).
3.1.2 dispensing
1) after carrying out being heated to 110 ± 5 DEG C by 3665g olive oil, by load weighted vitamin D2Powder is added thereto dissolving,
It is completely dissolved rear standby.
2) load weighted citric acid is added in appropriate 95% ethanol, is completely dissolved rear standby.
3) vitamin D after dissolving2Oil, oleovitamin A and citric acid ethanol, anisole are sequentially added in material-compound tank；
Plus vegetable oil, to the recipe quantity for specifying, medicine oil is stirred 3 hours.
4) please test, sample, inspection.It is standby after the assay was approved.
3.2 colloidal sols
1) gelatin, the G ＆ W of recipe quantity are weighed respectively, by glycerine and purified water addition glue pot, open stirring, and
It is warming up to 90 DEG C.
2) gelatin is blown slowly in addition glue pot while stirring, and is warming up to 80 DEG C, glue pot is vacuumized, period observation glue
Liquid liquid level rises situation, and glue pot exhaust outlet is opened according to glue height appropriateness, treats that vacuum valve is opened completely, and glue liquid level is no longer
Rise, when vacuum is not less than -0.06MPa and invariable vacuum, stops stirring and vacuumize, colloidal sol terminates.
3) clean 100 mesh spun silk cloth bags set is pricked in glue pot plastic emitting pipeline opening, slowly opens glue pot outlet valve
, be depressed into glue in the stainless steel insulation barrel of cleaning with compressed air by door；Connect heat-preserving container power supply (insulation barrel temperature setting 55 ±
5 DEG C), glue heat preservation for standby use.
3.3 pelletings, cold blowing, sizing
1) between the glue and medicine oil neck that will be prepared enter pelleting, according to intermediate products content detection result, calculate loading amount and
Content scope.
2) operated by full-automatic capsule and pill machine operational procedure.
3) open compressed air, in glue is flowed into expanding and arranging box by flexible pipe, start glue piece, adjust rubber thickness 70~
90.
4) after equipment debugging is qualified, according to the loading amount scope for calculating, pelleting is started.
5) capsule for pressing treats that capsule is approached in least significant end rotating cage through the incoming rotating cage of conveyer belt into cold blowing rotating cage between cold blowing
When 3/5, capsule in cold blowing rotating cage is transferred to sizing pallet.
6) capsule often placed in disk must not be more than the 1/3 of pallet height, and stir the capsule in pallet per hour, exchange
Change the upper and lower position of pallet.
7) rubber moisture content is determined between 15.0%~25.0%, you can terminate sizing.
8) sizing terminate rear capsule be transferred to heat dry between.
3.4 dry
1) capsule after cold blowing is shaped is transferred in hot rotating cage between drying, and is often saved inlet amount in rotating cage and be must not exceed 3/5, and often
Capsule is averagely placed in section rotating cage；The wiping ball cloth that will be immersed in 95% ethanol is gently wrung out, and is put into rotating cage, opens and turns
Cage, carries out scouring ball, removes the oil stain on surface.
2) after after the basic oil stains-less of capsule surface, taking-up speckles with the wiping ball cloth of 95% ethanol, in often section drying rotating cage again
It is put into dried and clean and wipes ball cloth.Start heat baking to be dried
3) treat that capsule is dried, clean, hand pinches flexible, rubber moisture content is 9.0%~11.0%, you can terminate heat drying
It is dry.
3.5 reason balls and packaging
To carry out picking ball on the resonable ball platform of dried capsule, the defective works such as seepage ball, big piller, special-shaped ball are picked
Go out, certified products are moved into the stainless steel cask of inner sleeve clean facilities pocket, packaging.
Following examples 2~17 can be carried out with reference to the preparation method of embodiment 1
The vitamin A ＆ D capsule type drops of embodiment 2
1st, content prescription：Every contains the unit of vitamin A 1500 and vitamin D2500 units
2nd, capsule prescription
Embodiment 3-dimensional gives birth to element AD capsule-type drops
1st, content prescription：Every contains the unit of vitamin A 1500 and vitamin D3500 units
2nd, capsule prescription
The vitamin A ＆ D capsule type drops of embodiment 4
1st, content prescription：Every contains the unit of vitamin A 1500 and vitamin D2500 units
2nd, capsule prescription
The vitamin A ＆ D capsule type drops of embodiment 5
1st, content prescription：Every contains the unit of vitamin A 1500 and vitamin D2500 units
2nd, capsule prescription
The vitamin A ＆ D capsule type drops of embodiment 6
1st, content prescription：Every contains the unit of vitamin A 1500 and vitamin D2500 units
2nd, capsule prescription
The vitamin A ＆ D capsule type drops of embodiment 7
1st, content prescription：Every contains the unit of vitamin A 1500 and vitamin D2500 units
Remarks：Embodiment 7 is that appropriate squalene is added in soybean oil so that content of the squalene in soybean oil
It is 458mg/100g
The vitamin A ＆ D capsule type drops of embodiment 8
1st, content prescription：Every contains the unit of vitamin A 1500 and vitamin D2500 units
2nd, capsule prescription
Remarks：Embodiment 8 is that appropriate squalene is added in soybean oil so that content of the squalene in soybean oil
It is 506mg/100g
The vitamin A ＆ D capsule type drops of embodiment 9
1st, prescription：Every contains the unit of vitamin A 1500 and vitamin D2500 units
2nd, capsule prescription
Remarks：Embodiment 8 is that appropriate squalene is added in soybean oil so that content of the squalene in soybean oil
It is 394mg/100g
The vitamin A ＆ D capsule type drops of embodiment 10
1st, content prescription：Every contains the unit of dehydroretinol 000 and vitamin D2700 units
2nd, capsule prescription
The vitamin A ＆ D capsule type drops of embodiment 11
1st, content prescription：Every contains the unit of vitamin A 1000 and vitamin D2500 units
2nd, capsule prescription
The vitamin A ＆ D capsule type drops of embodiment 12
1st, content prescription：Every contains the unit of vitamin A 5000 and vitamin D2500 units
2nd, capsule prescription
The vitamin A ＆ D capsule type drops of embodiment 13
1st, content prescription：Every contains the unit of vitamin A 1500 and vitamin D3500 units
2nd, capsule prescription
The vitaminAD soft capsule of embodiment 14
1st, content prescription：Every contains the unit of vitamin A 5000 and vitamin D2500 units
2nd, capsule prescription
The vitaminAD soft capsule of embodiment 15
1st, content prescription：Every contains the unit of vitamin A 5000 and vitamin D3500 units
2nd, capsule prescription
Embodiment 16
1st, content prescription：Every contains the unit of vitamin A 1500 and vitamin D2500 units
2nd, capsule prescription
Embodiment 17
1st, content prescription：Every contains the unit of vitamin A 1500 and vitamin D3500 units
2nd, capsule prescription
The vitamin D of embodiment 182Soft capsule
1st, content prescription：Every contains vitamin D25000 units (capsule loading amount 80mg)
2nd, capsule prescription
3rd, preparation method
3.1 dispensings
1) each supplementary material is weighed by recipe quantity.
2) after carrying out being heated to 110 ± 5 DEG C by olive oil, by load weighted vitamin D2Powder is added thereto dissolving, completely
It is standby after dissolving.
3) refining vegetable oil and anisole are weighed respectively by recipe quantity, with dissolve after vitamin D2Material-compound tank is added together
In, medicine oil is stirred 3 hours.
4) please test, sample, inspection.It is standby after the assay was approved.
3.2 colloidal sols
1) gelatin, the G ＆ W of recipe quantity are weighed respectively, by glycerine and purified water addition glue pot, open stirring, and
It is warming up to 90 DEG C.
2) gelatin is blown slowly in addition glue pot while stirring, and is warming up to 80 DEG C, glue pot is vacuumized, period observation glue
Liquid liquid level rises situation, and glue pot exhaust outlet is opened according to glue height appropriateness, treats that vacuum valve is opened completely, and glue liquid level is no longer
Rise, when vacuum is not less than -0.06MPa and invariable vacuum, stops stirring and vacuumize, colloidal sol terminates.
3) clean 100 mesh spun silk cloth bags set is pricked in glue pot plastic emitting pipeline opening, slowly opens glue pot outlet valve
, be depressed into glue in the stainless steel insulation barrel of cleaning with compressed air by door；Connect heat-preserving container power supply (insulation barrel temperature setting 55 ±
5 DEG C), glue heat preservation for standby use.
2.1.3 pelleting, cold blowing, sizing
1) between the glue and medicine oil neck that will be prepared enter pelleting, according to intermediate products content detection result, calculate loading amount and
Content scope.
2) operated by full-automatic capsule and pill machine operational procedure.
3) open compressed air, in glue is flowed into expanding and arranging box by flexible pipe, start glue piece, adjust rubber thickness 70~
90.
4) after equipment debugging is qualified, according to the loading amount scope for calculating, pelleting is started.
5) capsule for pressing treats that capsule is approached in least significant end rotating cage through the incoming rotating cage of conveyer belt into cold blowing rotating cage between cold blowing
When 3/5, capsule in cold blowing rotating cage is transferred to sizing pallet.
6) capsule often placed in disk must not be more than the 1/3 of pallet height, and stir the capsule in pallet per hour, exchange
Change the upper and lower position of pallet.
7) rubber moisture content is determined between 15.0%~25.0%, you can terminate sizing.
8) sizing terminate rear capsule be transferred to heat dry between.
2.1.4 dry
1) capsule after cold blowing is shaped is transferred in hot rotating cage between drying, and is often saved inlet amount in rotating cage and be must not exceed 3/5, and often
Capsule is averagely placed in section rotating cage；The wiping ball cloth that will be immersed in 95% ethanol is gently wrung out, and is put into rotating cage, opens and turns
Cage, carries out scouring ball, removes the oil stain on surface.
2) after after the basic oil stains-less of capsule surface, taking-up speckles with the wiping ball cloth of 95% ethanol, in often section drying rotating cage again
It is put into dried and clean and wipes ball cloth.Start heat baking to be dried.
3) treat that capsule is dried, clean, hand pinches flexible, rubber moisture content is 6%~10%, you can terminate drying.
2.1.5 ball is managed
To carry out picking ball on the resonable ball platform of dried capsule, the defective works such as seepage ball, big piller, special-shaped ball are picked
Go out, certified products are moved into the stainless steel cask of inner sleeve clean facilities pocket, then pack.
Following examples 19~21 can be carried out with reference to the preparation method of embodiment 18
The vitamin D of embodiment 193Soft capsule
1st, content prescription：Every contains vitamin D3400 units (capsule loading amount 80mg)
2nd, capsule prescription
The vitamin D of embodiment 202Soft capsule
1st, content prescription：Every contains vitamin D25000 units (capsule loading amount 80mg)
2nd, capsule prescription
The vitamin D of embodiment 213Soft capsule
1st, content prescription：Every contains vitamin D3400 units (capsule loading amount 80mg)
2nd, capsule prescription
The vitaminAD of embodiment 222Drops
1st, content prescription：Every gram contains the unit of vitamin A 5000 and vitamin D2500 units
2nd, preparation method
2.1 dispensings
1) the bucket heating water bath of vitamin A will be contained, controls 57~60 DEG C of bath temperature, until oleovitamin A is clarified
It is standby without being weighed again after visible crystallization.
2) after carrying out being heated to 110 ± 5 DEG C by 995g purified soyabean oils, by load weighted vitamin D2Powder is added thereto molten
Solution, is completely dissolved rear standby.
3) load weighted citric acid is added in appropriate 95% ethanol, is completely dissolved rear standby.
4) vitamin D after dissolving2Oil, oleovitamin A and citric acid ethanol, anisole, refining vegetable oil add successively
Enter in material-compound tank, medicine oil is stirred 3 hours.
5) please test, sample, inspection.It is standby after the assay was approved.
2.2 filling and packagings
1) each part of bottle placer is installed, syringe needle, silicone tube and peristaltic pump is connected, and silicone tube is accessed equipped with liquid
Container.
2) start bottle placer, adjust loading amount, loading amount is adjusted in acceptability limit, it is formal filling afterwards, then pack.
Following examples 23~24 can be carried out with reference to the preparation method of embodiment 22
The vitaminAD of embodiment 232Drops
1st, content prescription：Every gram contains the unit of vitamin A 5000 and vitamin D2500 units
The vitaminAD of embodiment 242Drops
1st, content prescription：Every gram contains the unit of vitamin A 5000 and vitamin D3500 units
First, the stability experiment research of vitamin D class preparation
1st, influence factor experiment：
The product of embodiment 1~24 is respectively placed in high temperature (60 DEG C) and illumination (5000Lx) is processed 30 days, foundation《China
Pharmacopeia》Four general rules of version in 2015 0721 and 0722 determine the content of corresponding vitamin A and D respectively, as a result such as following table：
Note：Compare with embodiment 6, P<0.05 shows as significant difference
2nd, stability test：
By the product of embodiment 1~24 difference accelerated test and long term test 6 months, foundation《Chinese Pharmacopoeia》Version in 2015
Four general rules 0721 and 0722 determine the content of corresponding vitamin A and D respectively, as a result such as following table：
Note：Compare with embodiment 6, P<0.05, show as significant difference.
3rd, experiment conclusion
By the comparative analysis of embodiment 1~9, as a result show that the vegetable oil containing squalene can significantly improve vitamin D class
The stability of preparation, the raising of this stability is relevant in the content of vegetable oil with squalene, when squalene is in vegetable oil
When content is 52~506mg/100g, squalene content is higher, and vitamin D class preparation stability is better.By embodiment 1, in fact
The comparative analysis of example 10~13 is applied to show：The raising of this stability does not change because the specification of vitamin D class preparation changes.This
Outward, also shown by embodiment 1, embodiment 14, embodiment 18 and the comparative study result of embodiment 23：The raising of this stability
Do not change because the formulation of vitamin D class preparation changes.
2nd, anti-infectives screening experiment research
1st, experimental technique
Healthy SD rat is randomly assigned embodiment 1~24, totally 24 groups, model is cut off using full thickness skin, 12 is small after wound
When after be grouped and force oral administration through stomach catheter, 1/day is continuous with 7 days, and granulation tissue is taken out after medication 7d.PDGF is adopted
After with Immunohistochemical Method and in situ hybridization, statistical procedures are carried out.
2nd, experimental result：
Remarks：Optical density is that (it is every section to take area according to the area ratio shared by the positive cell of certain gross area
On randomly select 5 visuals field), data withRepresent, and carry out statistical procedures, compare with embodiment 6,△P>0.05、★P<
0.01；Can not be defined with optical density because in situ hybridization section statining is heavier, therefore use section aobvious in 40 × 10 times of optics
Randomly select 5 visuals field under micro mirror, 100 cells are observed in each visual field, count positive cell number, data withRepresent, and
Statistical procedures are carried out, are compared with embodiment 6,△P>0.05、★P<0.01。
3rd, experiment conclusion
Shown with the comparative analysis of embodiment 6 by embodiment 1~5：The positive of 1~5PDGF of embodiment contents and PDGF is thin
The equal showed increased of born of the same parents' number, difference is statistically significant and the equal showed increased of the positive cell number of PDGF contents and PDGF.Table
It is bright to take the vitamin D class preparation containing squalene plant oil and increase required people's regulatory factor PDGF during skin healing
Content, have preferable facilitation to skin repair.Shown by embodiment 1, the comparative analysis of embodiment 10~13：It is this right
The facilitation of skin repair does not change because the specification of vitamin D class preparation changes.By embodiment 1, embodiment 14, implement
Example 18 and the comparative study result of embodiment 23 also show：This facilitation to skin repair is not because of vitamin D class preparation
Formulation changes and changes.Additionally, being shown with the comparative analysis of embodiment 1 by embodiment 7~9：The natural plant containing squalene
The vitamin D class preparation of oil just has the effect for promoting skin repair, exogenous addition squalene to the vitamin D class in vegetable oil
Preparation is to promoting skin repair effect unobvious.
3rd, anti-oxidation medicine screening experiment research
1st, DPPH methods
1) experimental principle
1,1- diphenyl -2- hardship diazanyl (1,1-diphenyl-2-picryhydrazyl (DPPH)) be a kind of stabilization with
Free radical centered on nitrogen, its ethanol solution shows purple, a length of 517nm of maximum absorption wave.When adding free radical in DPPH solution
During scavenger, when its lone pair electrons is paired, absorbs and disappear or weaken, cause solution colour to shoal, displaing yellow or faint yellow,
Absorbance at 517nm diminishes, and its intensity of variation is linear with radicals scavenging degree, therefore the method can use clearance rate table
Show, clearance rate is bigger, show that the material Scavenging activity is stronger.
2) preparation of solution
The preparation of 0.08mmol/L DPPH solution：Precision weighs DPPH8.0mg, with anhydrous alcohol solution and is settled to
In 200ml brown volumetric flasks, the DPPH solution that concentration is 0.004% is obtained, kept in dark place, it is standby.
3) experimental procedure
Embodiment solution (0.24,0.48,0.72,0.96,1.20mg/ml) 1.0ml of various concentrations is taken respectively, puts 10ml
In centrifuge tube, the DPPH solution of 3.0ml is added, room temperature lucifuge reacts 30min, while with absolute ethyl alcohol as blank, in 517nm ripples
Strong point determines light absorption value.DPPH free radical scavenging activities are calculated by following equation.
DPPH free radical scavenging activities (%)=A0-(As-Ac)/A0× 100%
In formula, A0The absorbance of -1.0ml distilled water+3.0mlDPPH solution
The absorbance of As -1.0ml sample solution+3.0mlDPPH solution
The absorbance of Ac -1.0ml sample solution+3.0ml absolute ethyl alcohols
To test in triplicate, try to achieve the average value of clearance rate.
2nd, salicylic acid method
1) experimental principle
Hydroxy radical is produced using Fenton reactions：H2O2+Fe2+=OH+H2O+Fe3+Bigcatkin willow is added in reaction system
Acid, the hydroxy radical and salicylism reaction of Fenton reaction generations, being created at 510nm has 2, the 3- dihydroxy benzenes of special absorption
Formic acid, reaction equation is as follows：If to the measured object with scavenging hydroxyl function is added in reaction system, generation will be reduced
Hydroxy radical so that the growing amount of colored compound is accordingly reduced.Using fixed reaction time methods, measured at 510nm
Absorbance containing measured object reaction solution, and compare with blank solution, to determine scavenging action of the measured object to hydroxy radical.
Its clearance rate computing formula is：Scavenging action to hydroxyl free radical (%)=A0- (Ax- Ax0)/A0·100
Wherein A0It is the light absorption value of blank, Ax is the light absorption value of sample-adding product, and Ax0 is to be not added with developer H2O2
2) experimental procedure
The addition of each solution first adds 9mmol/L FeSO successively according to shown in table 1 in colorimetric cylinder4, 9mmol/L second
Alcohol-salicylic acid, is subsequently added into appropriate amount of deionized water, is eventually adding 8.8mmol/LH2O2After shake up, after 37 DEG C of heating water bath 15min
Take out, survey its absorbance A0；A0During measure, reference solution is the system for being not added with hydrogen peroxide.As stated above, add shown in table 1
Each solution, carrys out mensuration absorbance Ax、Ax0；AxAnd Ax0During measure, reference solution is deionized water.
The scavenging hydroxyl experimental technique of table 1
3) preparation of reagents
Method is matched somebody with somebody in the acid of 9mmol/L alcohol-waters poplar：Claim 1.243g salicylic acids, ethanol dissolving is settled to 100mL, then dilutes 10
Times；9mmol/L ferrous sulfate matches somebody with somebody method：Claim 2.502gFeSO4·7H2O, deionized water dissolving is settled to 100mL, then dilutes 10
Times.8.8mmol/L H2O2With method：Claim 9.926g 30%H2O2, deionized water is settled to 100mL, then dilutes 100 times.
3rd, experimental result：
Note：Data withRepresent, and carry out statistical procedures, compare with embodiment 6,△P>0.05、★P<0.01。
4th, experiment conclusion
Showing embodiment 1~5 and the comparative analysis of embodiment 6 the vitamin D class preparation of the vegetable oil containing squalene has
Antioxidation；Content of the squalene in vegetable oil 206~395mg/100g vitamin D class preparation, antioxidation
Effect is the most obvious, and the vitamin D class preparation less than 52mg/100g, antioxidation is weaker.By embodiment 1, embodiment 10
~13 comparative analyses show：This antioxidation does not change because the specification of vitamin D class preparation changes.By embodiment 1,
Embodiment 14, embodiment 18 and the comparative study result of embodiment 23 also show：This antioxidation is not because of vitamin D class preparation
Formulation change and change.Additionally, also being shown with the comparative study result of embodiment 1 by embodiment 7~9：It is natural containing spiny dogfish
The vegetable oil vitamin D class preparation antioxidation of alkene is preferable, the vitamin D class system in exogenous addition squalene to vegetable oil
Agent, antioxidation is not obvious.
4th, anti-fatigue medicament screening experiment research
1st, experiment material
1) laboratory sample
Sample prepared by embodiment 1~24
2) experimental animal
From 18~22g of Male Kunming strain mice body weight that animal housing of Changchun Biological Products Institute, Ministry of Public Health provides
3) laboratory apparatus
Swimming trunk：50cm × 40cm × 60cm lucite grooves.
2nd, experimental technique
1) dosage determines
Test mice is only used as one group with every 4 at random, 24 groups are divided into by embodiment, 1/d of every mouse stomach amount connects
Continuous gavage 30d.
2) Loaned swimming test
Using 50cm × 40cm × 60cm lucite grooves, the depth of water about 35cm, 25 ± 0.5 DEG C of water temperature.Last gives tested
After medicine 30min, mouse forced swimming in swimming trunk, the sheet lead of the body weight of rat-tail root load 3% are put.Each tank during experiment
Be put into embodiment group mouse each every time, and carry out mark, record mouse from swim to the death time, as mouse trip
The swimming time (S).
3rd, experimental result：
| Embodiment | Walking weight load (S) | Conspicuousness (P values) |
| Embodiment 1 | 593.0±140.0 | P ＜ 0.05 |
| Embodiment 2 | 587.0±142.0 | P ＜ 0.05 |
| Embodiment 3 | 580.0±144.0 | P ＜ 0.05 |
| Embodiment 4 | 532.0±152.0 | P ＜ 0.05 |
| Embodiment 5 | 487.0±143.0 | P ＜ 0.05 |
| Embodiment 6 | 433.0±136.0 | --- |
| Embodiment 7 | 429.0±142.0 | --- |
| Embodiment 8 | 427.0±140.0 | --- |
| Embodiment 9 | 412.0±153.0 | --- |
| Embodiment 10 | 586.0±146.0 | P ＜ 0.05 |
| Embodiment 11 | 580.0±140.0 | P ＜ 0.05 |
| Embodiment 12 | 585.0±141.0 | P ＜ 0.05 |
| Embodiment 13 | 589.0±145.0 | P ＜ 0.05 |
| Embodiment 14 | 586.0±145.0 | P ＜ 0.05 |
| Embodiment 15 | 587.0±143.0 | P ＜ 0.05 |
| Embodiment 16 | 434.0±138.0 | --- |
| Embodiment 17 | 429.0±141.0 | --- |
| Embodiment 18 | 586.0±141.0 | P ＜ 0.05 |
| Embodiment 19 | 583.0±140.0 | P ＜ 0.05 |
| Embodiment 20 | 415.0±152.0 | --- |
| Embodiment 21 | 417.0±147.0 | --- |
| Embodiment 22 | 432.0±138.0 | --- |
| Embodiment 23 | 582.0±141.0 | P ＜ 0.05 |
| Embodiment 24 | 584.0±142.0 | P ＜ 0.05 |
Note：Data withRepresent, and carry out statistical procedures, compare with embodiment 6, P<0.05, show as conspicuousness poor
It is different.
4th, experiment conclusion
Showing embodiment 1~5 and the comparative analysis of embodiment 6 the vitamin D class preparation of the vegetable oil containing squalene has
Antifatigue effect；Content of the squalene in vegetable oil 206~395mg/100g vitamin D class preparation, antifatigue effect
Effect is the most obvious, and the vitamin D class preparation less than 52mg/100g, antifatigue effect is weaker.By embodiment 1, embodiment 10
~13 comparative analyses show：This antifatigue effect does not change because the specification of vitamin D class preparation changes.By embodiment 1,
Embodiment 14, embodiment 18 and the comparative study result of embodiment 23 also show：This antifatigue effect is not because of vitamin D class preparation
Formulation change and change.Additionally, also being shown with the comparative study result of embodiment 1 by embodiment 7~9：It is natural containing spiny dogfish
The vegetable oil vitamin D class preparation antifatigue effect of alkene is preferable, the vitamin D class system in exogenous addition squalene to vegetable oil
Agent, antifatigue effect is not obvious.
5th, the adverse reaction experimental study of exogenous addition squalene
1st, experiment material
1) laboratory sample
Sample prepared by embodiment 1~9
2) experimental animal
From 18~22g of Male Kunming strain mice body weight that animal housing of Changchun Biological Products Institute, Ministry of Public Health provides
2nd, experimental technique
1) dosage determines
Test mice is only used as one group with every 4 at random, 9 groups are divided into by embodiment, 1/d of every mouse stomach amount connects
Continuous gavage 30d.Rat food principle condition and behavior situation are monthly recorded during administration.
3rd, experiment conclusion
Result of study shows：Vitamin D class preparation in exogenous addition squalene to vegetable oil can cause diarrhea of mouse；
Squalene can cause mouse to occur appetite occur in various degree in the vitamin D class preparation of the content more than 458/100g of vegetable oil
Go down, body is become thin, the One's spirits are drooping and side effect such as be slow in action.
Finally illustrate, the above embodiments are merely illustrative of the technical solutions of the present invention and it is unrestricted, although with reference to compared with
Good embodiment has been described in detail to the present invention, it will be understood by those within the art that, can be to skill of the invention
Art scheme is modified or equivalent, and without deviating from the objective and scope of technical solution of the present invention, it all should cover at this
In the middle of the right of invention.
Claims (16)
1. a kind of vitamin D class preparation containing squalene plant oil, it is characterised in that the oil containing squalene plant includes natural
, it is semi-synthetic or artificial modification containing squalene plant oil.
2. it is according to claim 1 it is a kind of containing squalene plant oil vitamin D class preparation, it is characterised in that it is described to contain
Squalene content should be 52mg~506mg/100g in squalene plant oil.
3. it is according to claim 2 it is a kind of containing squalene plant oil vitamin D class preparation, it is characterised in that it is described to contain
Squalene content should be 206mg~458mg/100g in squalene plant oil.
4. it is according to claim 3 it is a kind of containing squalene plant oil vitamin D class preparation, it is characterised in that it is described to contain
Squalene content is 206mg~395mg/100g in squalene plant oil.
5. according to claim 2~4 any one containing squalene plant oil vitamin D class preparation, it is characterised in that
Described is natural oily containing squalene plant containing squalene plant oil.
6. it is according to claim 5 it is a kind of containing squalene plant oil vitamin D class preparation, it is characterised in that the day
The right oil containing squalene plant is the mixing of one or more in olive oil, palm oil, rice bran oil and amaranth rapeseed oil.
7. it is according to claim 6 it is a kind of containing squalene plant oil vitamin D class preparation, it is characterised in that the day
The right oil containing squalene plant is olive oil.
8. it is according to claim 1 it is a kind of containing squalene plant oil vitamin D class preparation, it is characterised in that the dimension
Raw element D classes preparation includes vitamin D single preparations of ephedrine and vitaminAD compound preparation.
9. it is according to claim 8 it is a kind of containing squalene plant oil vitamin D class preparation, it is characterised in that the dimension
Raw element D single preparationss of ephedrine are vitamin D2Or D3。
10. it is according to claim 8 it is a kind of containing squalene plant oil vitamin D class preparation, it is characterised in that the institute
It is A to state the vitamin A in vitaminAD compound preparation1, vitamin D is D2Or D3。
A kind of 11. vitamin D class preparations containing squalene plant oil according to claim 8, it is characterised in that the dimension
The I.U ratios of raw element A and vitamin D are 0.5~10:1.
12. a kind of vitamin D class preparations containing squalene plant oil according to claim 11, it is characterised in that described
The I.U ratios of vitamin A and vitamin D are 10:1、20:7 and 3:1.
13. a kind of vitamin D class preparations containing squalene plant oil according to claim 12, it is characterised in that described
Preparation is soft capsule, capsule-type drops and drops.
14. a kind of vitamin D class preparations containing squalene plant oil according to claim 13, it is characterised in that described
Preparation is the vitaminAD containing olive oil2Or vitaminAD3Capsule-type drops.
15. a kind of vitamin D class preparations containing squalene plant oil according to claim 13, it is characterised in that described
Preparation is the vitamin D containing olive oil2Or vitamin D3Capsule-type drops.
16. a kind of vitamin D class preparations containing squalene plant oil according to claim 13, it is characterised in that described
The preparation method of preparation is：In a heated condition, the active component of vitamin D class preparation is added to containing in squalene plant oil
Heating stirring makes it fully mix, i.e., the oil containing squalene plant is heated jointly with active component, and can be by outer in heating process
Power carries out lasting mixing to material, it is ensured that material dispersion is uniform, by thermal balance；Colloidal film is crossed when temperature is down to 25 DEG C, is made
Content, content is prepared into the vitamin D class preparation containing squalene plant oil by automatic rotary transformation of ownership capsule machine pressure.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110339162A (en) * | 2019-07-24 | 2019-10-18 | 杭州海王生物工程有限公司 | A kind of vitamins drops and preparation method thereof |
| CN110613696A (en) * | 2019-10-24 | 2019-12-27 | 人福普克药业（武汉）有限公司 | Ergocalciferol capsule and preparation method thereof |
| CN112675181A (en) * | 2020-11-19 | 2021-04-20 | 南京海鲸药业有限公司 | Vitamin D preparation containing linoleic acid vegetable oil |
| CN114009786A (en) * | 2021-11-22 | 2022-02-08 | 江南大学 | Nutritional oil composition for vitamin D delivery, preparation method and application |
| CN116270520A (en) * | 2023-03-03 | 2023-06-23 | 正大制药（青岛）有限公司 | Vitamin D capsule type drop and preparation method thereof |
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| CN105311037A (en) * | 2014-07-31 | 2016-02-10 | 山东达因海洋生物制药股份有限公司 | Vitamin D capsule type drops and preparation method thereof |
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| CN1371281A (en) * | 1999-08-31 | 2002-09-25 | 中外制药株式会社 | Soft capsules |
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| CN110339162A (en) * | 2019-07-24 | 2019-10-18 | 杭州海王生物工程有限公司 | A kind of vitamins drops and preparation method thereof |
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| CN112675181A (en) * | 2020-11-19 | 2021-04-20 | 南京海鲸药业有限公司 | Vitamin D preparation containing linoleic acid vegetable oil |
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| CN116270520A (en) * | 2023-03-03 | 2023-06-23 | 正大制药（青岛）有限公司 | Vitamin D capsule type drop and preparation method thereof |
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