CN101797259B - Compound vitamin nanoemulsion - Google Patents

Compound vitamin nanoemulsion Download PDF

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Publication number
CN101797259B
CN101797259B CN2010101241384A CN201010124138A CN101797259B CN 101797259 B CN101797259 B CN 101797259B CN 2010101241384 A CN2010101241384 A CN 2010101241384A CN 201010124138 A CN201010124138 A CN 201010124138A CN 101797259 B CN101797259 B CN 101797259B
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vitamin
fat
aeo
nanoemulsion
product
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CN101797259A (en
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陈鹏举
张光辉
吴华
赵庆枫
王汝都
胡梅
袁水霞
陈黎明
张国辉
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Henan Highlight Pharmaceutical Co ltd
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陈鹏举
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    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A40/00Adaptation technologies in agriculture, forestry, livestock or agroalimentary production
    • Y02A40/70Adaptation technologies in agriculture, forestry, livestock or agroalimentary production in livestock or poultry

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Abstract

The invention relates to compound vitamin nanoemulsion, belonging to the pharmaceutical technical field. the preparation method of the nanoemulsion per 1000ml comprises the following steps: fully mixing 150-240g of AEO-9 or AEO-4, 200-350g of Tween-80, 80-120g of benzyl alcohol and fat-soluble active ingredients at 30-60 DEG C to obtain oil phase, then adding water to dilute, and performing constant volume process, wherein the fat-soluble active ingredients comprises 60-180 million IU of vitamin A, 18-48 million IU of vitamin D and 25-75g of vitamin E, and vitamin K3 and dihydropyridine can be further added in the product. The product is clear and transparent, the average grain diameter is less than 10nm, the product has good dispersion stability; after nanoparticlization, vitamin A, D, Eand K has high efficiency and long-term effect and can be directly absorbed and used by the small intestine without bile, the absorptivity is 100%, and the bioavailability is about 98%. The product can be used in the livestock production; and even if the livestock and poultry have hepatic diseases or fat-absorbing disorders, the absorption of fat-soluble vitamins can not be affected, thus playinga very positive significance in improving the physique of livestock and poultry with diseases and shortening the treatment period.

Description

A kind of compound vitamin nanoemulsion
Technical field
The invention belongs to the pharmaceutical technology field, be specifically related to a kind of compound vitamin nanoemulsion, this nano-emulsion both can be oral as a kind of animal pharmaceuticals additive, can be used as again injection.
Background technology
Vitamin is requisite organic compound in people and the animal body metabolism, to metabolism and the growth promoter of body, keep body health and have important function.If certain vitamin of long-term lacking can cause the physiological function obstacle and certain disease occurs.Yet, body self can not synthetic vitamin or synthetic quantity less, need to from food, obtain or take vitamin replenisher.At present, the multidimensional product on the market is still take solid preparation as main, and the trend of oriented liquid dosage form development: be the poultry vitimin supplement with the premix material of solid multidimensional, usually need spice to feed, not only labor intensity is large, and is prone to the problem of mixing inequality; Liquid multi-dimensional then can mix drink, have easy to use, be easy to the advantages such as absorption.Yet existing liquid multi-dimensional generally is two kinds of liquid, and a kind of is the Water Soluble Compound multidimensional, and a kind of is fat-soluble A D oil, and the latter and Water Soluble Compound multidimensional float on the upper strata when composite, are difficult to dissolve each other.The another kind of form of existing liquid multi-dimensional then is conventional emulsion, although can overcome to a certain extent the defective of solid preparation, but still have the problem of the following aspects: the particle diameter of emulsion particle is larger, easily stops up the water fountain nipple, has created suitable Reproduction Conditions to pathogenic microorganism; Product stability is poor, and effect duration is generally December, during vitamin tire and can be reduced to 65% of labelled amount, and see that light color easily deepens, occurs turbid phenomenon; The poor compatibility of system is difficult to other beneficiating ingredients composite.
Summary of the invention
The object of the present invention is to provide a kind of compound vitamin nanoemulsion, this product clear, good stability, system has the compatibility of height, is easy to other water soluble preparations further composite.
Based on above-mentioned purpose, the present invention has adopted following technical scheme: a kind of compound vitamin nanoemulsion, every 1000ml nano-emulsion is prepared from by following method: get AEO-9 or AEO-4 150~240g, Tween-80 200~350g, benzyl alcohol 80~120g and fat-soluble effective ingredient and fully be mixed and made into oil phase under 30~60 ℃, then thin up, fixed molten; Described fat-soluble effective ingredient is: vitamin A 6000~18,000 ten thousand IU, vitamin D 31800~4,800 ten thousand IU, vitamin E 25~75g.
When sneaking into fat-soluble effective ingredient, preferentially add vitamin D 3And make it to dissolve.
Described fat-soluble effective ingredient is: vitamin A 6000~18,000 ten thousand IU, vitamin D 31800~4,800 ten thousand IU, vitamin E 25~75g, vitamin K 35~20g, dihydropyridine 10~30g.
Benzyl alcohol to 30~60 ℃ are heated first in preparation during oil phase, successively with dihydropyridine and vitamin D 3Be dissolved in and wherein add afterwards all the other fat-soluble effective ingredient, and then add AEO-9 or AEO-4 and Tween-80.Dihydropyridine and vitamin D 3Relatively indissoluble needs preferentially to add; Especially dihydropyridine, its dissolution velocity is slower, temporary transient muddiness may occur in the production, does not need to add surfactant this moment again.
Thin up, fixed molten before, add 2~5g n-butyl alcohol to system.N-butyl alcohol plays stabilizer function at this.
Institute's water is water for injection.
Compound vitamin nanoemulsion of the present invention is mainly used in replenishing the needed vitamin of body, prevention and treatment avitaminosis, and the suitable injection of doing, or adopt the directly mode administration of mixed drink.This product also can be used as semi-finished product and sells, and enterprise does further composite with water soluble vitamins for medicine.
The clarification of this product is bright, and mean diameter has good stably dispersing below 10nm: 1) 35 ℃ lower place VA content after 10 days be about 0 day 99.87%, the content of VE be 0 day 101.65%; After depositing 18 months, other component contents are all at more than 85.62% of its 0 day content.2) VA in the nano-emulsion has 11.4% destroyedly after placing 90 days under the illumination conditions of 4500lx ± 500lx approximately, and VE and other compositions are substantially constant.
Compound vitamin nanoemulsion of the present invention is efficient, long-acting, utilizes the medicine realeasing rate of dialysis-determined by ultraviolet spectrophotometry sample under 25 ℃, shows behind the 48h to have obvious slow releasing function up to 89.76%.
The present invention successfully is distributed to fatsoluble vitamin and dihydropyridine and makes nano-emulsion in the water, the greatly absorbance of improving product and bioavailability: body needs bile to participate in to the absorption of normality fat-soluble A, D, E, K, and be subjected to the factor affecting such as fat content in gastrointestinal physiology state and feed intake, the daily ration, absorbance only has 30~35%, and bioavailability is about 50%.And the nanorize processing makes the atomic number of vitamin particle surface more and more, caused the variation of vitamin particle surface electronics conformation and electron spectrum, make fat-soluble A, D, E, K become hydrophilicly by highly hydrophobic, and then greatly improved dissolubility, dispersibility and the dialysis performance of fatsoluble vitamin in water.Vitamin A. D. E in the nano-emulsion of the present invention, K can directly be absorbed by small intestinal, can contact rapidly and enter the intestinal mucosa cell with intestinal wall after in gastrointestinal, discharging, just can be absorbed in 2 hours, not need bile to participate in, absorbance 100%, bioavailability is about 98%.In herding was produced, even poultry suffer from hepatic disease or fat malabsorption is arranged, the absorption of fatsoluble vitamin can not be affected yet, and this has very positive meaning to body constitution, the Shorten the Treatment Process that promotes ill poultry.
Description of drawings
Fig. 1 is the photo of compound vitamin nanoemulsion of the present invention;
Fig. 2 is the photo of existing compound vitamin oral liquid.
The specific embodiment
Below in conjunction with specific embodiment, the present invention will be further described.
Embodiment 1
Every 1000ml compound vitamin nanoemulsion is prepared from by following method:
Get 95g benzyl alcohol, 200g AEO-4 and 280g Tween-80 and mix, be warming up to 40 ℃, successively with 30g dihydropyridine, 4,800 ten thousand IU vitamin D 3Be dissolved in wherein; Then add 9,000 ten thousand IU vitamin A, 50g vitamin E, 20g vitamin K 3Stir; Adding the 5g n-butyl alcohol to system stirs; Inject dilute with water, be dissolved to 1000ml.
Present embodiment product appearance clarification is bright, photo as shown in Figure 1, although the color of product can be slightly variant because of the difference of writing out a prescription, the clarity of products obtained therefrom of the present invention obviously is better than traditional product (Fig. 2).
Embodiment 2
Every 1000ml compound vitamin nanoemulsion is prepared from by following method:
Get 150g AEO-9,220g Tween-80 and be heated to 30 ℃, successively with 20g dihydropyridine, 3,000 ten thousand IU vitamin D 3Dissolving wherein; Add 7,500 ten thousand IU vitamin A, 32g vitamin E, 5g vitamin K 3Stir; Adding the 86g benzyl alcohol stirs; Inject dilute with water, be dissolved to 1000ml.
Embodiment 3
Every 1000ml compound vitamin nanoemulsion is prepared from by following method:
Get the 80g benzyl alcohol and be heated to 35 ℃, successively with 10g dihydropyridine, 1,800 ten thousand IU vitamin D 3Be dissolved in wherein; Add 6,000 ten thousand IU vitamin A, 25g vitamin E, 12g vitamin K 3Add 170g AEO-9,200g Tween-80; Add the 3g n-butyl alcohol to system; Inject dilute with water, be dissolved to 1000ml.
Embodiment 4
Every 1000ml compound vitamin nanoemulsion is prepared from by following method:
Get the 110g benzyl alcohol and be heated to 50 ℃, with 2,000 ten thousand IU vitamin D 3Dissolving wherein; Add 15,000 ten thousand IU vitamin A, the 60g vitamin E stirs; Adding 220g AEO-9,300g Tween-80 stirs; Inject dilute with water, be dissolved to 1000ml.
Embodiment 5
Every 1000ml compound vitamin nanoemulsion is prepared from by following method:
Get the 120g benzyl alcohol and be heated to 60 ℃, with forty-two million IU vitamin D 3Dissolving wherein; Add 18,000 ten thousand IU vitamin A, the 75g vitamin E stirs; Adding 240g AEO-4,350g Tween-80 stirs; Add the 2g n-butyl alcohol to system; Inject dilute with water, be dissolved to 1000ml.

Claims (4)

1. compound vitamin nanoemulsion, it is characterized in that, every 1000ml nano-emulsion is prepared from by following method: get AEO-9 or AEO-4 150~240g, Tween-80 200~350g, benzyl alcohol 80~120g and fat-soluble effective ingredient and fully be mixed and made into oil phase under 30~60 ℃, then thin up, fixed molten; Described fat-soluble effective ingredient is: vitamin A 6000~18,000 ten thousand IU, vitamin D 31800~4,800 ten thousand IU, vitamin E 25~75g when sneaking into fat-soluble effective ingredient, preferentially add vitamin D 3And make it to dissolve.
2. compound vitamin nanoemulsion, it is characterized in that, every 1000ml nano-emulsion is prepared from by following method: get AEO-9 or AEO-4 150~240g, Tween-80 200~350g, benzyl alcohol 80~120g and fat-soluble effective ingredient and fully be mixed and made into oil phase under 30~60 ℃, then thin up, fixed molten; Described fat-soluble effective ingredient is: vitamin A 6000~18,000 ten thousand IU, vitamin D 31800~4,800 ten thousand IU, vitamin E 25~75g, vitamin K 35~20g, dihydropyridine 10~30g; Benzyl alcohol to 30~60 ℃ are heated first in preparation during oil phase, successively with dihydropyridine and vitamin D 3Be dissolved in and wherein add afterwards all the other fat-soluble effective ingredient, and then add AEO-9 or AEO-4 and Tween-80.
3. compound vitamin nanoemulsion as claimed in claim 2 is characterized in that, thin up, fixed molten before, add 2~5g n-butyl alcohol to system.
4. compound vitamin nanoemulsion as claimed in claim 3 is characterized in that, institute's water is water for injection.
CN2010101241384A 2010-03-15 2010-03-15 Compound vitamin nanoemulsion Active CN101797259B (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103315957A (en) * 2013-06-27 2013-09-25 海南卫康制药(潜山)有限公司 Vitamin K1 lyophilized oral emulsion and preparation method thereof
CN103520101B (en) * 2013-10-14 2015-09-30 陕西科技大学 A kind of vitamin A nano-emulsion and preparation method thereof
CN103520102A (en) * 2013-10-14 2014-01-22 陕西科技大学 Vitamin D nano-emulsion and preparation method thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1236304A (en) * 1996-10-07 1999-11-24 弗·哈夫曼-拉罗切有限公司 Vitamin preparations for beverage applications
CN1568938A (en) * 2003-07-22 2005-01-26 范敏华 Nanometer emulsion and preparation method thereof
CN101637449A (en) * 2009-08-25 2010-02-03 曹金党 Nanometer vitamin self-microemulsion and preparation method thereof

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050220866A1 (en) * 2004-04-02 2005-10-06 Dr. Reddy's Laboratories Limited Novel capsule formulations of etoposide for oral use

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1236304A (en) * 1996-10-07 1999-11-24 弗·哈夫曼-拉罗切有限公司 Vitamin preparations for beverage applications
CN1568938A (en) * 2003-07-22 2005-01-26 范敏华 Nanometer emulsion and preparation method thereof
CN101637449A (en) * 2009-08-25 2010-02-03 曹金党 Nanometer vitamin self-microemulsion and preparation method thereof

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Inventor after: Zhang Guanghui

Inventor after: Wu Hua

Inventor after: Zhao Qingfeng

Inventor after: Wang Rudu

Inventor after: Hu Mei

Inventor after: Yuan Shuixia

Inventor after: Chen Liming

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Free format text: CORRECT: INVENTOR; FROM: CHEN PENGJU ZHANG GUANGHUI TO: CHEN PENGJU ZHANG GUANGHUI WU HUA ZHAO QINGFENG WANG RUDOU HU MEI YUAN SHUIXIA CHEN LIMING ZHANG GUOHUI

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Address after: 452570 16km away from G234 National Highway, Yuzhou City, Xuchang, Henan Province

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Address before: 461500 No. 783 Senyuan East Road, Changge City, Xuchang City, Henan Province

Patentee before: HENAN BRIGHT ANIMAL PHARMACEUTICAL CO.,LTD.