CN107714647A - A kind of oil-in-water type rubican nano-emulsion and preparation method thereof - Google Patents

A kind of oil-in-water type rubican nano-emulsion and preparation method thereof Download PDF

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Publication number
CN107714647A
CN107714647A CN201711139834.0A CN201711139834A CN107714647A CN 107714647 A CN107714647 A CN 107714647A CN 201711139834 A CN201711139834 A CN 201711139834A CN 107714647 A CN107714647 A CN 107714647A
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Prior art keywords
rubican
oil
surfactant
nano
emulsion
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CN201711139834.0A
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CN107714647B (en
Inventor
孙江宏
崔俊亚
高贵超
曲登峰
张颖
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Henan Muxiang Technology Co Ltd
Henan Soar Veterinary Pharmaceutical Co Ltd
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Henan Muxiang Technology Co Ltd
Henan Soar Veterinary Pharmaceutical Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/10Dispersions; Emulsions
    • A61K9/107Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/12Ketones
    • A61K31/122Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44Oils, 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

Abstract

The invention belongs to field of veterinary, specifically discloses a kind of oil-in-water type rubican nano-emulsion and preparation method thereof.It is made up of the composition of following weight/mass percentage compositions:Rubican 0.01~8.0%, surfactant 13~30%, cosurfactant 0~20%, oil 2.2~10.0%, surplus is water;Wherein, the surfactant is Tween 80, and the cosurfactant is absolute ethyl alcohol, and the oil is isopropyl myristate.Oil-in-water type rubican nano-emulsion of the present invention have the characteristics that viscosity is low, stability is good, it is dispersed it is strong, absorb rapid, targeting drug release, and the bioavilability of medicine can be improved, extend medicine half-life period in vivo, reduce toxic side effect;Oil-in-water type rubican nano-emulsion of the present invention also has the characteristics of surface tension is low, wellability is good, so medicine can be made to be attached to well on bacterium, penetrates into its metabolism of bacterium internal interference and plays antibacterial or bactericidal action.

Description

A kind of oil-in-water type rubican nano-emulsion and preparation method thereof
Technical field
The invention belongs to field of veterinary, and in particular to a kind of oil-in-water type rubican nano-emulsion and preparation method thereof.
Background technology
Rubican is a kind of material extracted from plant madder, and madder is a kind of time-honored vegetable colour, madder It is cold in nature enter blood system, can cooling blood and hemostasis, and can stagnation resolvation.The blood trouble that goes out of all blood-heat bleeding can be selected.Cooling and activating blood, dissolving stasis, stimulate the menstrual flow. For spitting blood, bleeding from five sense organs or subcutaneous tissue, metrostaxis, traumatism and bleeding, Amenorrhea stasis blocking, joint pain, tumbling and swelling.Cooling blood and hemostasis, promoting blood circulation: This product is stopped blooding without staying the stasis of blood, for heat symptom-complex bleeding, Amenorrhea stomachache, traumatic injury.
The rubican extracted from madder(C14H8O4)It is a kind of salmon pink crystal or ochre yellow powder, property under normal temperature and pressure Matter is stable, has excitant.Chinese is rubican, English name Alizarin.Alias name:1,2- dihydroxy -9, 10- amerantrones, 1,2- dihydroxy -1,2- dihydroxy castor quinone.Its physicochemical property, character salmon pink crystal or ochre yellow powder, it is close Degree(g/mL,20/4℃):1.06;Fusing point(℃):289.5;Boiling point(DEG C, normal pressure):430SU;Dissolubility:Be soluble in hot methanol and 25 DEG C of ether.Benzene, glacial acetic acid can be dissolved in, pyridine, carbon disulfide, be slightly soluble in water.
Growth of the rubican to staphylococcus aureus has inhibitory action, can suppress the penetrating of rat skin connective tissue Property, it is similar to rutin, there is antiinflammatory action;It is cosmetic colors and lipstick pigment, without any secondary work and it can be used safely With.But due to rubican in water it is insoluble, absorb not exclusively, bioavilability is low, Half-life in vivo is short, it is to heart in addition There is certain toxicity.Therefore, a kind of suitable formulation how is found so as to improve the bioavilability of rubican, targeting, delay The property released, extend its in vivo half-life period, heightening the effect of a treatment has become rubican and is urgently solved the problems, such as antibiotic substitute.
The content of the invention
The purpose of the present invention aims to provide a kind of oil-in-water type rubican nano-emulsion and preparation method thereof.
To achieve the above object, the technical scheme that the present invention takes is as follows:
A kind of oil-in-water type rubican nano-emulsion, is made up of the composition of following weight/mass percentage compositions:
Rubican 0.01~8.0%, surfactant 13~30%, cosurfactant 0~20%, oil 2.2~10.0%, surplus are Water;Wherein, the surfactant is Tween-80, and the cosurfactant is absolute ethyl alcohol, and the oil is different for myristic acid Propyl ester (IPM).
Preparation method, step are as follows:
(1), form by weight/mass percentage composition, weigh rubican, surfactant, cosurfactant, oil, water, it is standby;
(2), first rubican is completely dissolved in cosurfactant and surfactant, after stirring, add oil, stir Mix;Finally it is added dropwise water, is stirred continuously while dropwise addition, until forming the system of homogeneous transparent, produces oil-in-water type rubican Nano-emulsion.
The specifically used method and dosage of the rubican nano-emulsion of the present invention:Mixed drink, 65kg is watered with the mL of this product 100, is supplied Livestock and poultry are freely drunk, and are used in conjunction 3 days.Points for attention:This product is only used for drinking water, not injectable, could be used after must being watered mixing, no Can directly it use, laying cycle of laying hens disabling.
The present invention has advantages below:
1. oil-in-water type rubican nano-emulsion of the present invention has, viscosity is low, stability is good, it is dispersed it is strong, absorb rapid, targeting and release The features such as medicine, and the bioavilability of medicine can be improved, extend medicine half-life period in vivo, reduce toxic side effect;
2. oil-in-water type rubican nano-emulsion of the present invention also has the characteristics of surface tension is low, wellability is good, so can make medicine It is attached to well on bacterium, penetrates into its metabolism of bacterium internal interference and play antibacterial or bactericidal action.
Embodiment
Technical scheme is described in further detail below in conjunction with specific embodiment, but the protection model of the present invention Enclose and be not limited thereto.
Embodiment 1
Prescription:Rubican 1.2g, surfactant 6.0g, cosurfactant 4.0g, oily 2.5g, water 13.6g;Wherein, it is described Surfactant is Tween-80, and the cosurfactant is absolute ethyl alcohol, and the oil is isopropyl myristate (IPM).
Preparation method:
(1), form by weight/mass percentage composition, weigh rubican, surfactant, oil, water, it is standby;
(2), first rubican is completely dissolved in cosurfactant and surfactant, after stirring, add oil, stir Mix;Finally it is added dropwise water, is stirred continuously while dropwise addition, until forming the system of homogeneous transparent, produces oil-in-water type rubican Nano-emulsion.
Reference examples 1
Prescription:Rubican 0.01g, surfactant 13.38g, oily 2.43g, water 84.18g;Wherein, the surfactant is APEO (40) rilanit special(RH40), the oil is isopropyl myristate (IPM).
Preparation method:
(1), form by weight/mass percentage composition, weigh rubican, surfactant, oil, water, it is standby;
(2), first rubican is completely dissolved in surfactant, after stirring, add oil, stir and evenly mix;Finally it is added dropwise Water, it is stirred continuously while dropwise addition, until forming the system of homogeneous transparent, produces oil-in-water type rubican nano-emulsion.
Reference examples 2
Prescription:Rubican 0.03g, surfactant 9.0g, oily 1.0g, water 20g;Wherein, the surfactant is polyoxy second Alkene ether (40) rilanit special(RH40), the oil is isopropyl myristate (IPM).
Preparation method is the same as reference examples 1.
Reference examples 3
Prescription:Rubican 0.3g, surfactant 9.0g, cosurfactant 4.0g, oily 1.0g, water 25.7g;Wherein, it is described Surfactant is APEO (40) rilanit special(RH40), the cosurfactant is 1,2-PD, described Oil is isopropyl myristate (IPM).
Preparation method is the same as embodiment 1.
Reference examples 4
Prescription:Rubican 0.5g, surfactant 9.81g, cosurfactant 3.27g, oily 1.36g, water 21.47g;Wherein, The surfactant is APEO (40) rilanit special(RH40), the cosurfactant is 1,2-PD, The oil is isopropyl myristate (IPM).
Preparation method is the same as embodiment 1.
Reference examples 5
Prescription:Rubican 0.9g, surfactant 15.0g, cosurfactant 5.0g, oily 2.2g, water 36.9g;Wherein, institute It is Tween-80 to state surfactant, and the cosurfactant is absolute ethyl alcohol, and the oil is isopropyl myristate (IPM).
Preparation method is the same as embodiment 1.
Reference examples 6
Prescription:Rubican 0.9g, surfactant 15.0g, cosurfactant 5.0g, oily 5.0g, water 34.1g;Wherein, institute It is Tween-80 to state surfactant, and the cosurfactant is absolute ethyl alcohol, and the oil is ethyl oleate.
Preparation method is the same as embodiment 1.
Reference examples 7
Prescription:Rubican 0.9g, surfactant 7.5g, cosurfactant 5.0g, oily 1.4g, water 18.5g;Wherein, it is described Surfactant is Tween-80, and the cosurfactant is absolute ethyl alcohol, and the oil is isopropyl myristate (IPM).
Preparation method is the same as embodiment 1.
Reference examples 8
Prescription:Rubican 1.0g, surfactant 7.5g, cosurfactant 5.0g, oily 1.4g, water 15.0g;Wherein, it is described Surfactant is Tween-80, and the cosurfactant is absolute ethyl alcohol, and the oil is isopropyl myristate (IPM).
Preparation method is the same as embodiment 1.
Reference examples 9
Prescription:Rubican 1.0g, surfactant 6.0g, cosurfactant 4.0g, oily 1.1g, water 15.0g;Wherein, it is described Surfactant is Tween-80, and the cosurfactant is absolute ethyl alcohol, and the oil is ethyl oleate.
Preparation method is the same as embodiment 1.
Reference examples 10
Prescription:Rubican 1.2g, surfactant 7.5g, cosurfactant 5.0g, oily 1.4g, water 15.0g;Wherein, it is described Surfactant is Tween-80, and the cosurfactant is absolute ethyl alcohol, and the oil is isopropyl myristate (IPM).
Preparation method is the same as embodiment 1.
Reference examples 11
Prescription:Rubican 1.3g, surfactant 6.0g, cosurfactant 4.0g, oily 1.1g, water 9.4g;Wherein, it is described Surfactant is Tween-80, and the cosurfactant is absolute ethyl alcohol, and the oil is ethyl acetate.
Preparation method is the same as embodiment 1.
Stability test
1. high speed centrifugation
The rubican nano-emulsion prepared is taken in centrifuge tube, its property is observed again after centrifuging 20 min with 12000r/min rotating speed Shape, it the results are shown in Table 1.
2. temperature stability test
The rubican nano-emulsion prepared is fitted into transparent flint glass bottle, seals, be positioned over 4 DEG C, room temperature(25℃)With Keep sample under 60 DEG C of three kinds of temperature conditionss and investigate each 60d, sampled every 10d and observe its character, the results are shown in Table 2-4.
As seen from the above table:No matter high speed centrifugation or temperature stability test are passed through using the nano-emulsion of prescription of the present invention, Clear is kept, has no the unstable demulsifying phenomenons such as layering, the precipitation of muddy or crystal, it is seen that be a kind of medicine of stabilization Formulation.On the contrary, unstable demulsifying phenomenon is occurred using nano-emulsion obtained by the prescription of reference examples, solution is muddy or is layered, body It is unstable.

Claims (2)

1. a kind of oil-in-water type rubican nano-emulsion, it is characterised in that be made up of the composition of following weight/mass percentage compositions:
Rubican 0.01~8.0%, surfactant 13~30%, cosurfactant 0~20%, oil 2.2~10.0%, surplus are Water;Wherein, the surfactant is Tween-80, and the cosurfactant is absolute ethyl alcohol, and the oil is different for myristic acid Propyl ester.
A kind of 2. method for preparing oil-in-water type rubican nano-emulsion as claimed in claim 1, it is characterised in that step is as follows:
(1), form by weight/mass percentage composition, weigh rubican, surfactant, cosurfactant, oil, water, it is standby;
(2), first rubican is completely dissolved in cosurfactant and surfactant, after stirring, add oil, stir Mix;Finally it is added dropwise water, is stirred continuously while dropwise addition, until forming the system of homogeneous transparent, produces oil-in-water type rubican Nano-emulsion.
CN201711139834.0A 2017-11-16 2017-11-16 Oil-in-water type alizarin nanoemulsion and preparation method thereof Active CN107714647B (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102302449A (en) * 2011-08-25 2012-01-04 西北农林科技大学 Oil-in-water cinnamic aldehyde nano emulsion medicament
CN104027408A (en) * 2014-05-14 2014-09-10 河南牧翔动物药业有限公司 Oil-in-water type compound apramycin nano-emulsion
CN104352566A (en) * 2014-10-21 2015-02-18 河南牧翔动物药业有限公司 Oil-in-water compound chlortetracycline nanoemulsion
CN104642312A (en) * 2015-02-13 2015-05-27 兰州大学 Rheum officinale free anthraquinone composition for preventing plant powdery mildew and nano emulsion preparation

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102302449A (en) * 2011-08-25 2012-01-04 西北农林科技大学 Oil-in-water cinnamic aldehyde nano emulsion medicament
CN104027408A (en) * 2014-05-14 2014-09-10 河南牧翔动物药业有限公司 Oil-in-water type compound apramycin nano-emulsion
CN104352566A (en) * 2014-10-21 2015-02-18 河南牧翔动物药业有限公司 Oil-in-water compound chlortetracycline nanoemulsion
CN104642312A (en) * 2015-02-13 2015-05-27 兰州大学 Rheum officinale free anthraquinone composition for preventing plant powdery mildew and nano emulsion preparation

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