CN1732902A - Vitamin contained spray - Google Patents
Vitamin contained spray Download PDFInfo
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- CN1732902A CN1732902A CN 200510097943 CN200510097943A CN1732902A CN 1732902 A CN1732902 A CN 1732902A CN 200510097943 CN200510097943 CN 200510097943 CN 200510097943 A CN200510097943 A CN 200510097943A CN 1732902 A CN1732902 A CN 1732902A
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Abstract
The invention relates to a vitamin contained spray, wherein the medicinal liquor contains one or several kinds of vitamins, greasy medicinal liquid carrying consisting one or several synthesized or natural fatty oils. The prepared spray has good stability and atomizing property.
Description
[technical field]
The invention belongs to medical technical field, relate to a kind of spray, particularly relate to the spray that contains vitamin substances.
[background technology]
All kinds of vitamins preparations that version pharmacopeia in 2000 of China's current are recorded mainly contain tablet, injection, soft capsule, drop etc., as vitamin A soft gelatin capsule, vitamin AD soft gelatin capsule, vitamin AD drop, vitamin D2 soft gelatin capsule, vitamin E sheet, vitamin E injection etc.
In the oral formulations of vitamin substances, particularly in the oral formulations of fatsoluble vitamin, soft gelatin capsule and drop are more common dosage forms, as the Yi Kexin that sells in Chinese market
Soft capsule, vitamin A And D drops
Soft capsule, Themgran Junior
Drop etc.But the shortcoming of these dosage forms is conspicuous:
(1) soft capsule production equipment complexity: conventional vitamin AD soft gelatin capsule is a soft capsule, and " Yi Kexin " of Weihai dyne is the soft capsule of water droplet shape, and these two kinds capsular production process controls are complicated, and need more special equipment, production cost height;
(2) chew and inconvenience is swallowed in use: in fact the child is many swallows software food could successfully chewing more than 1 years old, and it is difficult require 1 years old children's to chew swallowing.But the health doctor advises that usually the baby just begins to take vitamin AD behind full moon.The dosage of China pharmaceutical control and administration department regulation is (drop): children's once-a-day, below an one full year of life, retinol1 500 units, Vitamin D5. 00 unit (about 3～4); 1～3 one full year of life, dehydroretinol 000 unit, vitamin D 700 units (about 4～5); 3～6 one full year of life, dehydroretinol 500 units, vitamin D 800 units (about 6～7); The above increase as one feels fit of 6 one full year of life;
(3) divided dose is inaccurate: when using drop, factors such as scale dropper and dropping liquid environment all can exert an influence to dosage, and this does not also consider the part that children's spues, and resembles Yi Kexin
This drop, after medicinal liquid was extruded, the residual volume in each capsule all can be different.Having is exactly that the medicine liquid volume of existing vitamin AD preparation is bigger again, uses Themgran Junior as 1 years old children's
Daily dose be 1ml, every Yi Kexin
The content amount 0.35g that weighs, and be oil solution, be very easy to spue or flow out, influenced the accuracy of dosage;
(4) sensory issues: existing vitamin AD preparation is a solvent with cod-liver oil or vegetable oil all, and volume is bigger, although medicinal liquid adopts the spice taste masking, but still is difficult to overcome the greasy feeling of medicinal liquid;
(5) stability problem: the chemical stability of vitamin A own and vitamin D is just bad, uses vegetable oil further to increase the unstable factor of medicinal liquid in the preparation, and medicinal liquid becomes sour easily, spoiled even generation precipitation.
For this reason, develop a kind of production process simple, chew and use that to swallow convenience, good mouthfeel, the divided dose preparation that contains vitamin substances accurate, that have good stability be very significant.Spray is a kind of extraordinary technical scheme.
U.S. Mayor drugmaker has successfully developed dozens of vitamin spray based on a U.S. Pat 4525341 in 1985, sells well on American market over nearly 20 years, just because of this dosage form advantage of spray.Although the vitamin spray product of Mayor company is recorded on the famous handbook that instructs entire United States doctor medication " doctor's handbook (PDR) on the desk " for years, but, the medicinal liquid carrier that these proprietary preparations use is ethanol, aqueous alcohol or water, embodiment is the medicinal liquid carrier with the ethanol (200proof spirit) of concentration nearly 100% then, this technical scheme is defective, shows:
(1) making the medicinal liquid carrier with high concentration ethanol is responsive to some use crowd;
When (2) making water be carrier, (when particularly fatsoluble vitamin exists) as a rule, medicinal liquid may form heterogeneous dispersive Emulsion, those skilled in the art know, this is a kind of drug system of physical instability, this also is why to use Tween-80 as emulsifying agent, to reach the more reason of steady statue in the embodiment.
The technical scheme of the disclosed vitamin spray of Chinese patent application (CN1061720A) and U.S. Pat 4525341 basically identicals.
For another example, it is the vitamin A Emulsion of solvent based on water that United States Patent (USP) (US4170229) discloses a kind of, is used for head diseases such as spraying treatment head pruritus.International monopoly (WO0109000) discloses a kind of based on the polymeric vitamin E spray of Cyclomethicone.And U.S. Patent application (USPA20040175461) discloses a kind of vitamin spray, and the vitamin of use amount is sprayed on the food with day, and it is more convenient to it is said that this spray uses.
Over more than 20 year, people are contained in exploitation aspect the spray of vitamin, and the main starting point is that with dehydrated alcohol, ethanol-water mixture or water be the solvent carrier, and many products of putting on market are the solvent carrier with dehydrated alcohol still mainly.
As everyone knows, ethanol, aqueous alcohol or water, their viscosity is lower.This is useful for spray, and extremely important, promptly will obtain quantitatively to spray accurately, spout do not block, and just requires the viscosity of medicinal liquid lower.Solution in this explanation spray should have suitable, lower viscosity.
As vitamin substances, the solvent of fatsoluble vitamin spray particularly is useful for the dissolving of medicine with ethanol.But because ethanol has volatility, medicinal liquid passes in the liquid pipeline and may concentrate at atomizing pump, causes spout to block and can not successfully spray; Also may cause the first spray drug dose to descend because of atomizing pump passes the ducted medicinal liquid volatilization of liquid, this be disadvantageous for drug delivery system.
Certainly, containing the alcohol of debita spissitudo, also is useful such as containing the ethanol that is lower than 40% (w/w) to the hygiology stability of product, promptly can suppress growth of microorganism effectively.On the other hand, because ethanol has the effect of certain blood vessel dilating, adding a spot of ethanol in spray is useful for improving the infiltration rate of medicine on the spraying mucosa.
Like this, with vitamin substances, fatsoluble vitamin particularly, make contain that low concentration (or not containing) ethanol, the lower viscosity that is suitable for spraying, medication are convenient, divided dose accurately, safe spray is very significant when having good stability, produce, storing and transporting and using.That is to say, with vitamin, fatsoluble vitamin particularly, be mixed with solution, pass through the effect of mechanical pump (as aerosol apparatus or nebulizer) power again, with the preparation (being the vitamin spray) of medicinal liquid atomisation, just become this area scientific worker's goal in research.
For this reason, the purpose of this invention is to provide a kind of vitamin substances that contains, the spray of fatsoluble vitamin particularly, its medicinal liquid has a kind of like this character, be that drug use is convenient, the viscosity of its medicinal liquid is low, and divided dose is accurate, even medicine is after storage after a while, the first spray amount of medicine still can reach the active medicine of required dosage (or design dosage).
The present invention also aims to provide a kind of vitamin substances that contains, the spray of fatsoluble vitamin particularly, the alcohol amount low (or not containing alcohol) that contains of this spray, thereby be applicable to the patient that should not use alcohol formulations above-mentioned, medicinal liquid is little to the zest of agents areas such as mucosa, and toxicity is low.And the safety of preparation in production, storage, transportation and use is better.
The discovery that the inventor is pleasantly surprised, use low viscous synthetic or natural fatty oil, particularly medium chain length fatty acid triglyceride is a solvent, preparation contains vitamin substances, the spray of fatsoluble vitamin particularly, can successfully realize the present invention, and the product that makes have good stable and sprayable performance.This is that prior art can not be led and teaches.
[summary of the invention]
The present invention is a kind of spray of the vitamin substances that contains, particularly fatsoluble vitamin, this spray by:
(1) contain the physiologically active ingredient vitamin substances medicinal liquid and
(2) sprayer unit of forming by hand spray pump and bottle
Two parts are formed.
As everyone knows, sprayer unit wherein is requisite as spray.Therefore technical characterictic of the present invention is medicinal liquid, with what doubt is not, this technical characterictic prolongs and sprayer unit, and term promptly of the present invention " spray " both can refer to the spraying system that medicinal liquid and sprayer unit are formed, and also can singly refer to medicinal liquid.Based on the spraying system that medicine passes on, each spray amount is calculated by the medicinal liquid of spraying out, can be between 20-500mg, and preferred, each spray amount is between 40-250mg.
" vitamin substances " that is used for indication of the present invention refers to now to find or the synthetic vitamins biological active substances of having come out from nature.Comprise followingly, but be not limited to the vitamin of following kind:
Retinoid: comprise the isomer, polymer of vitamin A, vitamin A, their alcohol, their carboxylate etc., be found in fish oil, egg yolk and the vegetable that its shortage can cause nyctalopia and epithelial tissue pathological changes.Vitamin A is typically arranged
1, vitamin A
2, vitamin A ethyl ester, vitamin A palmitate, beta-carotene etc. and other retinoids are like thing.
Vitamin(e) B group: comprise vitamin B
1(thiamine), vitamin B
2(riboflavin), vitamin B
6(pyridoxol class), nicotinic acid, pantothenic acid, biotin, inositol, folic acid, vitamin B
12(comprising cobalamin, hydroxocobalamin, mecobalamin, cobamamide etc.) etc. and other vitamin(e) B groups are like thing.
Vitamin C: have another name called ascorbic acid, also comprise sodium ascorbate.
The vitamin D class: be found in fish oil, egg yolk, its shortage can cause rickets.Comprise vitamin D
1, vitamin D
2, vitamin D
3Deng and their analog.
Vitamin E class: comprise alpha-tocopherol (α-tocopherol), betatocopherol, Gamma-Tocopherol, Delta-Tocopherol etc., and alpha-tocopherol amine (α-tocotriend), betatocopherol amine, Gamma-Tocopherol amine, Delta-Tocopherol amine etc., and other vitamin E analog.
Vitamin(e) G: i.e. vitamin B
2(riboflavin).
Biotin: i.e. biotin.
Vitamin K class: be present in green vegetables, the flesh of fish, have coagulant blood, prevent the hemorrhage effect of Denging, mainly contain two kinds of forms, i.e. vitamin Ks
1And vitamin K
2Be also shown in vitamin K
3, vitamin K
4
The Citrin class: be a kind of mixture of flavonoid, be present in Sucus Citri Reticulatae, Fructus Capsici, its shortage can cause that the permeability of capillary wall increases, thereby causes hemorrhage probability to increase, and claims citrin again.
Preferably, " vitamin substances " of indication of the present invention is meant fatsoluble vitamin, includes but not limited to vitamin A and analog thereof, vitamin D and analog thereof, vitamin E and analog thereof, vitamin K and analog thereof.
Preferred, " vitamin substances " of indication of the present invention is meant vitamin A
1, vitamin A
2, the carboxylate of retinoid material, vitamin D
1, vitamin D
2, vitamin D
3, alpha-tocopherol, betatocopherol, vitamin K
1, vitamin K
2
The present invention contains the spray of vitamin substances, in its medicinal liquid, comprising:
(1) one or more vitamin substances and
(2) oleaginous medicinal liquid carrier is comprising one or more synthetic or natural fatty oils.
Above-mentioned " medicinal liquid carrier ", in the pharmaceutics field, its definition is clear and definite, promptly forms the main material of medicament, or main adjuvant, and the physicochemical property of medicament is played an important role.Such as in the present invention, oil medicinal liquid carrier (fatty oil) makes medicinal liquid have lower viscosity simultaneously and has important function dissolved substance, is to realize critical material of the present invention.Same understanding easily, this carrier consumption very much, reasonable definite method is that the final volume during according to the preparation preparation determines that this is the general knowledge of preparation industrial circle.
Above-mentioned oleaginous medicinal liquid carrier can be that all can be used as medicinal neutral oil.
Preferably, above-mentioned oil medicinal liquid carrier is the fatty glyceride with medium chain, is often referred to have C
6～C
14The fatty glyceride of chain length.
More preferably, refer to C
8～C
12Fatty glyceride; As to have C
8～C
12The fatty glyceride of satisfied fatty acid preparation, as one or more the mixture in medium chain acid glycerol one ester, medium chain acid triglyceride, the medium chain triglyceride, wherein the former two is referred to as medium chain acid glycerol part ester, English MediumChain Partial Glycerides by name.More preferably available medium chain triglyceride (is called for short MCT, GTCC; European Pharmacopoeia name medium Chain Triglycerides; Japanese Pharmacopoeia name Caprylic/CapricTriglyceride).
Medium chain acid glycerol part ester can be selected the product I MWITOR of German SASOL company for use
742.
Medium chain triglyceride can be used the product MIGLYOL available from German CONDEA chemical company (CONDEA ChemieGmbH)
812 or MIGLYOL
810; Or available from the product LABRAFAC CC of French GATTEFOSSE company; Or available from the product A LDO of U.S. LONZA company
MCT.The product of these different brands is at sad (C
8) and capric acid (C
10) the ratio aspect difference is arranged slightly, as MIGLYOL
812 contain sad 50～65%, capric acid 30～45%; MIGLYOL
810 contain sad 65～80%, capric acid 20～35%; LABRAFAC CC contains sad 50～80%, capric acid 20～50%; ALDO
MCT contains sad 65～80%, capric acid 20～35%.But they are basic identical aspect physicochemical properties such as acid number, saponification number, iodine number, hydroxyl value, viscosity, freezing point, moisture, and the difference of two kinds of fatty acid proportions can not produce significantly influence to preparation nature.Certainly, be to allow to exist with a spot of other fatty acids of the conceptual understanding of " impurity " in the pharmaceutical field, this is conceptive and without prejudice to spirit of the present invention.
Above-mentioned oleaginous medicinal liquid carrier can also be natural fatty oil, can contain a spot of undersaturated fatty acid in this fatty oil.The fatty oil that contains the unsaturated fatty acid of more amount can reduce the amount of unsaturated fatty acid by hydrogenation.Preferred natural fat oil is Oleum Brassicae campestris.
Oleaginous medicinal liquid carrier of the present invention, its key factor is that they have lower viscosity, and this is to realize a key factor of the present invention, because for spray, have only medicinal liquid to have lower viscosity, could successfully spray, just can make the amount of liquid medicine unanimity of each ejection.
The present invention contains the spray of vitamin substances, except that comprising vitamin substances and oleaginous medicinal liquid carrier, can also comprise increasing the deliquescent solvent of vitamin substances, as hydroxyl alcohol, preferably ethanol in its medicinal liquid.
Further, the present invention contains the spray of vitamin substances, can also contain the additives that are selected from correctives class, antioxidant class, surfactant-based, viscosifier class on a small quantity in its medicinal liquid.
Described correctives class can be improved the product taste, as menthol, Oleum menthae, milk chocolate essence (as the BFL1227 type, International Flavors﹠amp; Fragrances company product), sorbitol etc.
Described antioxidant class can improve the product chemical stability, as to hydroxyl tert-butyl group methoxybenzene (BHA), toluene di-tert-butyl phenol (BHT) etc.
The described surfactant-based dissolubility that increases medicine makes medicinal liquid even, as tween 80, Arlacel-80 etc.
Described viscosifier class, the viscosity that can regulate medicinal liquid make medicinal liquid have best spray effect, as glycerol, propylene glycol, polyvinylpyrrolidone (PVP) etc. to desired extent.
Owing to use the oil medicinal liquid carrier of fatty wet goods, therefore the material of sprayer unit of the present invention (comprising spray bottle and atomizing pump) can be selected from one or more the combination in high density polyethylene (HDPE), polypropylene, metal (as aluminum), the glass etc., thereby can make medicament obtain better stability.
In addition, each spray amount of spray is generally 20～500mg, preferred 40～250mg, and these can be according to the medication needs, select to buy the manual pump (or claiming valve system) of suitable specification from the market and realize, as the quantitative atomizing pump of German Fei Fu company (Pfeiffer).
The present invention contains the spray of vitamin substances, by 100ml, comprises in its medicinal liquid:
(1) 0.1mg～25g vitamin substances;
(2) add to the oil medicinal liquid carrier of 100ml.
Definitely, the present invention contains the spray of vitamin substances, by 100ml, comprises in its medicinal liquid:
(1) 0.1mg～25g vitamin substances,
(2) 0～40g ethanol,
(3) 0～10g medicinal additives,
(4) add to the oil medicinal liquid carrier of 100ml;
Described medicinal additive is selected from correctives class, antioxidant class, surfactant-based, viscosifier class.
In order to prepare the spray solution of homogeneous, use under the alcoholic acid situation at needs, above-mentioned ethanol should control water content, and promptly concentration of alcohol should be greater than 95%, and preferably, described ethanol is dehydrated alcohol.
More preferably, the present invention contains the spray of vitamin substances, by 100ml, comprises in its medicinal liquid:
(1) 0.5mg～15g vitamin substances,
(2) 0～30g ethanol,
(3) 0～5g medicinal additives,
(4) add to the oil medicinal liquid carrier of 100ml;
Described medicinal additive is selected from correctives class, antioxidant class, surfactant-based, viscosifier class.
Preparation the present invention contains the spray of vitamin substances, can or be suspended in the oil medicinal liquid carrier the vitamin substances dissolving, add ethanol or other pharmaceutical addition agent etc. in case of necessity, make the medicinal liquid dissolving, medicinal liquid filters with filter (as sintered glass filter, microporous filter membrane) in case of necessity, again with liquid medicine filling in the high density polyethylene (HDPE) spray bottle, screw the hand spray pump (as the selection standard atomizing pump, 0.1ml, screw thread 18/415, Germany Pfeiffer company China portion provides), promptly.
Above preparation method is not limited by the preparation process, and is self-evident, and other technical processs that are of value to preparation are also within category of the present invention.
The product of the spray that contains vitamin substances of the present invention's preparation, can investigate its pharmaceutics character by the following method:
1. spraying uniformity: the horizontal direction spraying, observe spray discharge pattern and uniformity thereof.
2. medicinal liquid volatile quantity: spray bottle and atomizing pump that the spray of medicinal liquid will be housed screw, and keep sealing state, spray 10 times, after confirming that spraying is normal, in 40 ℃ calorstat, placed 3 months, take by weighing the weight of spray before and after placing, be calculated as follows the medicinal liquid volatile quantity.10 bottles of replications are asked the calculation meansigma methods.
" bottle weight in the formula
*" be the average weight (n=10) of the sprayer unit formed by spray bottle and atomizing pump.
3. the 1st discharge rate difference: get the spray that contains vitamin substances, spray 10 times, confirm that spraying is normal, spray is placed the room temperature place again, place after 7 days, precision takes by weighing the 1st spray weight, spray 10 times, precision takes by weighing 10 times gross weight again, calculates every spray average weight; Be calculated as follows the diversity factor of the 1st discharge rate.10 bottles of replications are asked the calculation meansigma methods.
4. maximum discharge rate difference: get the spray that contains vitamin substances, spray 10 times, remove, after confirming that spraying is normal, spray 10 times, precision takes by weighing the gross weight of each weight and 10 times, calculates every spray average weight again, be calculated as follows the discharge rate difference of single, thereby try to achieve the maximum discharge rate difference in the spraying 10 times.
5. the relative concentration of vitamin A: spray bottle and atomizing pump that the spray of medicinal liquid will be housed screw, keep sealing state, in 40 ℃ calorstat, placed 3 months, according to " Pharmacopoeia of People's Republic of China (version was two ones in 2005) " appendix VII J " vitamin A algoscopy ", measure in the medicinal liquid of spray 0 month and the concentration of the vitamin A in March, with 0 month concentration was 100%, the relative percent of the concentration of vitamin A in the medicinal liquid when calculating March is the relative concentration of 40 ℃ of vitamin A when preserving March.Promptly as shown in the formula calculating:
6. the relative concentration of vitamin D: according to vitamin D in " Pharmacopoeia of People's Republic of China (version was two ones in 2005) " the 672nd～674 page
2And vitamin D
3And the assay method under their the preparation item is measured content; Test method and result processing method are with above the 5th " relative concentration of vitamin A ".
7. the relative concentration of vitamin E: according to vitamin E and preparation item assay method mensuration content down thereof in " Pharmacopoeia of People's Republic of China (version was two ones in 2005) " the 674th～675 page; Test method and result processing method are with above the 5th " relative concentration of vitamin A ".
8. vitamin K
1Relative concentration: according to vitamin K in " Pharmacopoeia of People's Republic of China (version was two ones in 2005) " the 676th page
1And the assay method under the preparation item is measured content; Test method and result processing method are with above the 5th " relative concentration of vitamin A ".
Because the present invention contains fatty oil in the spray of vitamin substances to skin and mucosa nonirritant, even eye also has good tolerability to this fatty oil, and the pure content in the product is low, perhaps do not contain alcohol, so the toxicity of product is low, safety good.
By spray of the present invention, its viscosity is low, and volatility is low, and spraying is even, and divided dose is accurate, has good stability.The first spray amount of medicine can reach the active medicine of design dosage more than 90%.It is low to contain the alcohol amount, does not perhaps contain alcohol, is applicable to the patient that some should not use alcohol formulations, and the safety of preparation in production and storage is good.
[specific embodiment]
The invention provides a kind of spray that contains vitamin substances.Below be described in further detail the present invention by specific embodiment, but and unrestricted the present invention.
Embodiment 1
Prescription:
Vitamin A 0.3g
LABRAFAC CC adds to 100ml
Preparation method:
Get vitamin A, add the LABRAFAC CC of 50ml, stirring and dissolving adds LABRAFAC CC to 100ml, filters with exsiccant G6 sintered glass filter, divides to install in the aerosol container, screws atomizing pump, promptly.
Embodiment 2
Prescription:
Vitamin A acetate 0.35g
Vitamin D
25mg
Oleum menthae 0.5g
LABRAFAC CC adds to 100ml
Preparation method:
Get vitamin A acetate, vitamin D
2, LABRAFAC CC and the Oleum menthae of adding 80ml, stirring and dissolving adds LABRAFAC CC to 100ml, filters with exsiccant G6 sintered glass filter, divides to install in the aerosol container, screws atomizing pump, promptly.
Embodiment 3
Prescription:
Vitamin D
315mg
Beta-carotene 1g
Oleum menthae 0.7g
Milk chocolate essence 1g
LABRAFAC CC adds to 100ml
Preparation method:
Get vitamin D
3And beta-carotene, LABRAFAC CC, Oleum menthae and the milk chocolate essence of adding 50ml, stirring and dissolving adds LABRAFAC CC to 100ml, filters with exsiccant G6 sintered glass filter, divides to install in the aerosol container, screws atomizing pump, promptly.
Embodiment 4
Prescription:
Vitamin E 25g
IMWITOR 742 8g
Oleum menthae 1g
Milk chocolate essence 4g
Oleum Brassicae campestris 10g
LABRAFAC CC adds to 100ml
Preparation method:
At room temperature, get vitamin E, add LABRAFAC CC, IMWITOR 742, Oleum Brassicae campestris, Oleum menthae and the milk chocolate essence of 30ml, stirring and dissolving adds LABRAFAC CC to 100ml, divides to install in the aerosol container, screws the hand spray pump, promptly.
Embodiment 5
Prescription:
Vitamin K
110g
Dehydrated alcohol 30g
1,2-propylene glycol 9.5g
Menthol 0.5g
Toluene di-tert-butyl phenol 0.02g
MIGLYOL 810 adds to 100ml
Preparation method:
Get vitamin K
1, adding ethanol, propylene glycol, menthol, toluene di-tert-butyl phenol, stirring and dissolving adds MIGLYOL 810 to 100ml, divides to install in the aerosol container, screws the hand spray pump, promptly.
Embodiment 6
Prescription:
Vitamin A palmitate 0.5g
Vitamin D
25mg
Vitamin D
30.5mg
Vitamin E 15g
Vitamin K
15g
Toluene di-tert-butyl phenol (BHT) 0.02g
To hydroxyl tert-butyl group methoxybenzene (BHA) 0.05g
Tween 80 0.5g
Oleum menthae 0.5g
98% ethanol 20g
LABRAFAC CC adds to 100ml
Preparation method:
Get vitamin A palmitate, vitamin D
2, vitamin D
3, vitamin E, vitamin K
1, add dissolve with ethanol, add the LABRAFAC CC of Oleum menthae, dibenzylatiooluene, butylated hydroxyarisol, tween 80 and 30ml, stirring and dissolving adds LABRAFAC CC to 100ml, divides to install in the aerosol container, screws the hand spray pump, promptly.
Embodiment 7
Prescription:
Vitamin A 0.4g
Vitamin B
10.4g
Vitamin B
20.5g
Vitamin B
61g
Vitamin B
12(cobalamin) 0.1mg
Vitamin C 0.1g
Vitamin D
22.5mg
Vitamin D
32.5mg
Vitamin E 5g
Vitamin K
12g
Vitamin K
30.5g
Nicotiamide 50mg
Nicotinic acid 50mg
Folic acid 100mg
Beta-carotene 0.3g
Menthol 0.5g
95% ethanol 40g
LABRAFAC CC adds to 100ml
Preparation method:
Get various vitamin, nicotiamide, nicotinic acid, folic acid, beta-carotene, add dissolve with ethanol, the LABRAFAC CC that adds menthol, dibenzylatiooluene, butylated hydroxyarisol and 30ml, stirring and dissolving, add LABRAFAC CC to 100ml, divide to install in the aerosol container, screw the hand spray pump, promptly.
Reference examples 1---contain the spray of vitamin A with reference to 1 preparation of the embodiment in the United States Patent (USP) (US4525341)
Prescription:
Vitamin A 0.3g
Glycerol 2g
Tween 80 0.16g
Dehydrated alcohol adds to 100ml
Preparation method:
Get vitamin A, glycerol, tween 80, the adding dehydrated alcohol is an amount of, and stirring and dissolving adds ethanol to 100ml, filters with exsiccant G6 sintered glass filter, divides to install in the aerosol container, screws atomizing pump, promptly.
Reference examples 2---contain the spray of vitamin A, vitamin D with reference to 1 preparation of the embodiment in the United States Patent (USP) (US4525341)
Prescription:
Vitamin A acetate 0.35g
Vitamin D
25mg
Glycerol 2g
Tween 80 0.16g
Oleum menthae 2g
Dehydrated alcohol adds to 100ml
Preparation method:
Get vitamin A acetate, vitamin D
2, glycerol, tween 80 and Oleum menthae, add dehydrated alcohol 60ml, stirring and dissolving adds ethanol to 100ml, filters with exsiccant G6 sintered glass filter, branch installs in the aerosol container, screws atomizing pump, promptly.
Reference examples 3---contain multivitamin spray with reference to 1 preparation of the embodiment in the United States Patent (USP) (US4525341)
Prescription:
Vitamin A 0.4g
Vitamin B
10.4g
Vitamin B
20.5g
Vitamin B
61g
Vitamin B
12(cobalamin) 0.1mg
Vitamin C 0.1g
Vitamin D
22.5mg
Vitamin D
32.5mg
Vitamin E 5g
Vitamin K
12g
Vitamin K
30.5g
Nicotiamide 50mg
Nicotinic acid 50mg
Folic acid 100mg
Beta-carotene 0.3g
Glycerol 2g
Tween 80 0.16g
Menthol 1.5g
95% ethanol adds to 100ml
Preparation method:
Get various vitamin, nicotiamide, nicotinic acid, folic acid, beta-carotene, glycerol, tween 80 and menthol, add ethanol 80ml, stirring and dissolving adds ethanol to 100ml, divides to install in the aerosol container, screws the hand spray pump, promptly.
Experimental example 1---galenic pharmacy character is investigated
Investigate 7 embodiment samples and 3 reference examples samples according to preceding method, all use the atomizing pump of 0.1ml, measure spraying uniformity, 40 ℃
*The medicinal liquid volatile quantity in March, room temperature are placed the 1st discharge rate difference after 7 days, maximum discharge rate difference, 40 ℃
*(sample of embodiment 1,2,6,7 and reference examples 1,2,3 is all measured the ester of vitamin A or vitamin A to the vitamin relative concentration in March, the sample determination vitamin D of embodiment 3, the sample determination vitamin E of embodiment 4, the sample determination vitamin K of embodiment 5).The results are shown in Table 1.
The galenic pharmacy character of table 1 sample is investigated the result
| Sample | The spraying uniformity | 40℃ *The medicinal liquid volatile quantity in March | The 1st discharge rate difference | Maximum discharge rate difference | 40℃ *The vitamin relative concentration in March |
| Embodiment 1 | Spraying is even, and droplet is tiny | 0.73％ | 96.6％ | 4.6％ | VA＝97.1％ |
| Embodiment 2 | Spraying is even, and droplet is tiny | 0.11％ | 94.1％ | 5.7％ | VA ester=96.4% |
| Embodiment 3 | Spraying is even, and droplet is tiny | -0.67％ | 93.7％ | 3.9％ | VD 3＝97.9％ |
| Embodiment 4 | Spraying is even, and droplet is tiny | -0.49％ | 95.4％ | 4.8％ | VE＝98.2％ |
| Embodiment 5 | Spraying is even, and droplet is tiny | 0.68％ | 92.9％ | 5.4％ | VK 1＝96.3％ |
| Embodiment 6 | Spraying is even, and droplet is tiny | 0.29％ | 94.6％ | 6.3％ | VA ester=95.3% |
| Embodiment 7 | Spraying is even, and droplet is tiny | -0.44％ | 93.8％ | 4.2％ | VA ester=95.9% |
| Reference examples 1 | Spraying is even, and droplet is tiny | -2.82％ | 88.4％ | 5.7％ | VA＝93.1％ |
| Reference examples 2 | Spraying is even, and droplet is tiny | -2.38％ | 84.2％ | 6.1％ | VA ester=93.7% |
| Reference examples 3 | Spraying is even, and droplet is tiny | -2.64％ | 87.5％ | 4.8％ | VA＝94.3％ |
From measurement result as seen, aerosol spray of the present invention is even, droplet is tiny, at polyethylene is to preserve in the sprayer unit formed of the spray bottle of material and atomizing pump, it is good to place after 3 months product stability in 40 ℃ the calorstat, first discharge rate and every spray average magnitude are approaching, and maximum discharge rate difference is little, and divided dose is accurate.
Experimental example 2---the spraying uniformity is investigated
The medicinal liquid of embodiment 1～7 is packed in the spray bottle, and every bottle of 15ml (20ml spray bottle) sprays with the atomizing pump of 0.05ml, 0.1ml respectively, the uniformity of relatively spraying and maximum discharge rate difference.The results are shown in Table 2.
The spraying uniformity of table 2 different size atomizing pump is investigated the result
| Sample | The atomizing pump model | The spraying uniformity | Maximum discharge rate difference |
| Embodiment 1 | 0.05ml pump | Spraying is solid cone shaped, and droplet is evenly distributed, and drop is tiny | 5.8％ |
| 0.10ml pump | Spraying is solid cone shaped, and droplet is evenly distributed, and drop is tiny | 4.6％ | |
| Embodiment 2 | 0.05ml pump | Spraying is solid cone shaped, and droplet is evenly distributed, and drop is tiny | 5.3％ |
| 0.10ml pump | Spraying is solid cone shaped, and droplet is evenly distributed, and drop is tiny | 4.9％ | |
| Embodiment 3 | 0.05ml pump | Spraying is solid cone shaped, and droplet is evenly distributed, and drop is tiny | 6.5％ |
| 0.10ml pump | Spraying is solid cone shaped, and droplet is evenly distributed, and drop is tiny | 4.4％ | |
| Embodiment 4 | 0.05ml pump | Spraying is solid cone shaped, and droplet is evenly distributed, and drop is tiny | 5.8％ |
| 0.10ml pump | Spraying is solid cone shaped, and droplet is evenly distributed, and drop is tiny | 5.6％ | |
| Embodiment 5 | 0.05ml pump | Spraying is solid cone shaped, and droplet is evenly distributed, and drop is tiny | 4.4％ |
| 0.10ml pump | Spraying is solid cone shaped, and droplet is evenly distributed, and drop is tiny | 4.6％ | |
| Embodiment 6 | 0.05ml pump | Spraying is solid cone shaped, and droplet is evenly distributed, and drop is tiny | 5.9％ |
| 0.10ml pump | Spraying is solid cone shaped, and droplet is evenly distributed, and drop is tiny | 5.4％ | |
| Embodiment 7 | 0.05ml pump | Spraying is solid cone shaped, and droplet is evenly distributed, and drop is tiny | 5.1％ |
| 0.10ml pump | Spraying is solid cone shaped, and droplet is evenly distributed, and drop is tiny | 5.7％ |
As seen, spray of the present invention all can obtain uniform spray effect with the atomizing pump spraying of different model, and maximum discharge rate difference is basically identical also, and divided dose is accurate.
Although the present invention has carried out description to a certain degree, significantly, under the condition that does not break away from the spirit and scope of the present invention, can carry out the variation of component condition etc.Be appreciated that to the invention is not restricted to described embodiment, and belong to the scope of claim, it comprises the replacement that is equal to of described each factor.
Claims (10)
1. spray that contains vitamin substances, contain in its medicinal liquid:
(1) one or more vitamin substances and
(2) oil medicinal liquid carrier;
Described oil medicinal liquid carrier is made up of one or more synthetic or natural fatty oil.
2. by the described spray of claim 1, also contain ethanol in its medicinal liquid.
3. by claim 1 or 2 described sprays, also contain the additives that are selected from correctives class, antioxidant class, surfactant-based, viscosifier class in its medicinal liquid.
4. by any described spray in the claim 1～3,, contain in its medicinal liquid by 100ml:
(1) 0.1mg～25g vitamin substances,
(2) 0～40g ethanol,
(3) 0～10g medicinal additives are selected from correctives class, antioxidant class, surfactant-based, viscosifier class,
(4) add to the oil medicinal liquid carrier of 100ml.
5. by the described spray of claim 4,, contain in its medicinal liquid by 100ml:
(1) 0.5mg～15g vitamin substances,
(2) 0～30g ethanol,
(3) 0～5g medicinal additives are selected from correctives class, antioxidant class, surfactant-based, viscosifier class,
(4) add to the oil medicinal liquid carrier of 100ml.
6. by any described spray in the claim 1～5, wherein said vitamin substances is to be selected from the vitamin of retinoid, vitamin(e) B group, vitamin C, vitamin D class, vitamin E class, vitamin K apoplexy due to endogenous wind and their analog.
7. by any described spray in the claim 1～5, wherein said vitamin substances is to be selected from vitamin A and analog, vitamin D and analog thereof, vitamin E and analog thereof, vitamin K and analog thereof.
8. by any described spray in the claim 1～5, wherein said oil medicinal liquid carrier is C
8～C
12The mixture of one or more in the monoglyceride of fatty acid, diester or three esters.
9. by any described spray in the claim 1～5, wherein said oil medicinal liquid carrier mainly is a caprylic/capric triglyceride.
10. by any described spray in the claim 1～5, wherein said oil medicinal liquid carrier is an Oleum Brassicae campestris.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510097943 CN1732902A (en) | 2005-09-01 | 2005-09-01 | Vitamin contained spray |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510097943 CN1732902A (en) | 2005-09-01 | 2005-09-01 | Vitamin contained spray |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1732902A true CN1732902A (en) | 2006-02-15 |
Family
ID=36075658
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200510097943 Pending CN1732902A (en) | 2005-09-01 | 2005-09-01 | Vitamin contained spray |
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| Country | Link |
|---|---|
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1957890B (en) * | 2006-10-17 | 2010-06-23 | 颜怀伟 | Composite vitamine product for local increasing fat safely, and fabricating method |
| CN105193723A (en) * | 2015-10-23 | 2015-12-30 | 郑州泰丰制药有限公司 | Doxercalciferol spray preparation and preparation method thereof |
| CN105492081A (en) * | 2013-05-29 | 2016-04-13 | 博格有限责任公司 | Using Vitamin D to Prevent or Reduce Chemotherapy-Induced Hair Loss |
| CN107982300A (en) * | 2017-12-07 | 2018-05-04 | 青岛九远医疗科技有限公司 | A kind of spray and its preparation method and application |
| US11305016B2 (en) | 2009-08-14 | 2022-04-19 | Berg Llc | Vitamin D3 and analogs thereof for treating alopecia |
-
2005
- 2005-09-01 CN CN 200510097943 patent/CN1732902A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1957890B (en) * | 2006-10-17 | 2010-06-23 | 颜怀伟 | Composite vitamine product for local increasing fat safely, and fabricating method |
| US11305016B2 (en) | 2009-08-14 | 2022-04-19 | Berg Llc | Vitamin D3 and analogs thereof for treating alopecia |
| CN105492081A (en) * | 2013-05-29 | 2016-04-13 | 博格有限责任公司 | Using Vitamin D to Prevent or Reduce Chemotherapy-Induced Hair Loss |
| CN112156097A (en) * | 2013-05-29 | 2021-01-01 | 博格有限责任公司 | Use of vitamin D for preventing or reducing chemotherapy-induced alopecia |
| CN105193723A (en) * | 2015-10-23 | 2015-12-30 | 郑州泰丰制药有限公司 | Doxercalciferol spray preparation and preparation method thereof |
| CN107982300A (en) * | 2017-12-07 | 2018-05-04 | 青岛九远医疗科技有限公司 | A kind of spray and its preparation method and application |
| CN107982300B (en) * | 2017-12-07 | 2021-04-20 | 青岛九远医疗科技有限公司 | Spray and preparation method and application thereof |
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