CN100998592B - Microemulsion containing matrine - Google Patents
Microemulsion containing matrine Download PDFInfo
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- CN100998592B CN100998592B CN200710036208A CN200710036208A CN100998592B CN 100998592 B CN100998592 B CN 100998592B CN 200710036208 A CN200710036208 A CN 200710036208A CN 200710036208 A CN200710036208 A CN 200710036208A CN 100998592 B CN100998592 B CN 100998592B
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- matrine
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Abstract
A microemulsion of matrine with high biologic utilization rate and stability is proportionally prepared from matrine, emulsifier, emulsifying aid, oil phase and water phase. Its preparing process is also disclosed.
Description
Technical field
The present invention relates to medical technical field, is a kind of novel form----microemulsion and preparation method thereof of matrine.
Background technology
Matrine is to extract the quinolizidine kind alkaloid obtain from Chinese medicine Radix Sophorae Flavescentis, Radix Sophorae Tonkinensis, Herba Sophorae alopecuroidis, has effects such as antibiotic, antiinflammatory, antitumor, antiallergic, arrhythmia, swelling diuretic, immunity and biological respinse adjusting.Matrine has dosage forms such as injection, tablet, capsule, liposome, gel now, and the matrine injection is usually used in treating diseases such as hepatitis B, viral hepatitis, tumor; The matrine oral formulations has the enhancing body anti-cancer ability, alleviates effects such as chemotherapy toxic side effect; The matrine transdermal administration can be treated skin allergic disease, be improved the scar tissue hypertrophy of skin etc.But there are problems such as targeting is not strong, the target organ drug level is low in injection; The oral formulations half-life is short, gastrointestinal side effect is high, significant first pass effect is arranged; Conventional preparation capable of permeating skin also exist action time short, administration number of times is frequent, medicine skin transmitance is crossed shortcomings such as low.
Summary of the invention
The objective of the invention is to overcome the prior art above shortcomings, a kind of matrine administration novel form------microemulsion containing matrine and preparation method thereof is provided.
The microemulsion containing matrine oral administration, can make the medicine absorption in vivo reach the peak fast, eliminate slow, blood concentration fluctuation is little, the medicine body-internal-circulation time is long, helps the absorption of medicine; The microemulsion containing matrine drug administration by injection can improve stability of drug, improves the drug level in target organ, target tissue, the target cell, the circulation time of significant prolongation medicine in blood; The microemulsion containing matrine transdermal administration can be accelerated the dissolution rate of medicine, increases keratodermatitis flowability of cell membranes and permeability, thereby has improved the transdermal diffusion rate of medicine.And the microemulsion preparation method is simple, is convenient to store, and has good stability, and is easy to suitability for industrialized production.
Technical scheme of the present invention is as follows:
Microemulsion containing matrine is made up of medicine and substrate.Medicine is a matrine, and substrate is become to be grouped into for four kinds by oil phase, water, emulsifying agent and co-emulsifier.Wherein, oil phase is selected from olive oil, single glyceryl linoleate, ethyl acetate, oleic acid, isopropyl myristate; Emulsifying agent is selected from soybean phospholipid, caprylic/capric polyethyleneglycol glyceride; Co-emulsifier is selected from Tween 80, polysorbas20, ethanol; Water is a deionized water.The component of medicine and proportioning are: matrine 1-5% (g/g), emulsifying agent 4-15% (g/g), co-emulsifier 6-16% (g/g), oil phase 6-15% (g/g), water 50-70% (g/g).
The preparation method of microemulsion containing matrine of the present invention adopts following steps:
1, manual dripping method, mix deionized water and co-emulsifier and be (I) mutually, mix oil phase and emulsifying agent and be (II) mutually, medicine is added to (II) mutually in for the pastille inner phase, under 40 ℃ continue to be stirred with the speed of 1ml/min the pastille inner phase is dropwise added (I) mutually in, form clear and bright pastille microemulsion.
2, the even method of ultrasonic breast, mix deionized water and co-emulsifier and be (I) mutually, mix oil phase and emulsifying agent and be (II) mutually, medicine is added to (II) mutually in for the pastille inner phase, under lasting the stirring, the pastille inner phase is mixed mutually with (I), under the power of 250w, ultrasonic breast is spared 30min with mixture, gets the pastille microemulsion.
3, the even method of high pressure homogenize breast, mix deionized water and co-emulsifier and be (I) mutually, mix oil phase and emulsifying agent and be (II) mutually, medicine being added to (II) is the pastille inner phase in mutually, under lasting the stirring pastille inner phase being mixed mutually with (I), is 6 * 10 with mixture at a step valve pressure
6Pa-7 * 10
6Pa (60-70bar), secondary valve pressure are 6 * 10
7Pa-7 * 10
7Under the Pa (600-700bar), even 3-5 time of homogenized milk gets the pastille microemulsion.
The microemulsion particle size range that makes by above method about 100nm (90-110nm), size is even, outward appearance is clear and bright.
The inventor has carried out the test of microemulsion containing matrine effect, adopting body weight is that the Wistar rat of 200-250g is as laboratory animal, microemulsion containing matrine and matrine water solution with same medicine content carry out oral respectively, injection, transdermal administration, collect every data of medicine internal metabolism kinetic determination medicine internal metabolism, through data compilation, statistical method carries out data analysis, compare with matrine water solution as can be known, microemulsion containing matrine possesses oral back absorption in vivo really, and to reach the peak fast, eliminate slow, blood concentration fluctuation is little, the advantage that the body-internal-circulation time is long; Can improve drug level, the circulation time of significant prolongation medicine in blood in target organ, the target tissue behind the drug administration by injection; Transdermal administration can accelerate medicine dissolution rate, reduce the fluctuation of medicine bulk concentration.
The present invention is prepared into microemulsion with matrine, pass through drug administration by injection, adjuvants such as isopropyl myristate in the preparation and lecithin are nontoxic to human body, biodegradation and absorption in vivo, thereby and can improve the circulation time of medicine in blood system, increase the concentration of medicine in target organ and tissue and improve drug effect; By oral administration, surfactant can reduce surface tension, the obstacle when overcoming medicine by the gastrointestinal tract epithelial cell film, and medicine is easy to be delivered to absorption site by the gastrointestinal wall hydrated sheath, has improved dissolution and permeability; Pass through percutaneous drug delivery, microemulsion can increase the dissolubility of insoluble drug, form higher Concentraton gradient, promote drug absorption, microemulsion hydrophobic part and horny layer interact, and disturb the lipid bilayer structure, but hydrophilic segment aquation horny layer, both combineds effect can strengthen medicine at cuticular permeability, are beneficial to drug osmotic and absorb.In sum, this invention provides a kind of novel form for the clinical practice of matrine.
Description of drawings
Fig. 1 is the pastille microemulsion particle size distribution figure of microemulsion containing matrine high pressure homogenization method preparation among the embodiment 1
Fig. 2 is the pastille microemulsion particle size distribution figure of the even method preparation of the ultrasonic breast of microemulsion containing matrine among the embodiment 1
Fig. 3 is the pastille microemulsion particle size distribution figure of the manual dripping method preparation of microemulsion containing matrine among the embodiment 2.
Fig. 4 is the pastille microemulsion particle size distribution figure of the even method preparation of the ultrasonic breast of microemulsion containing matrine among the embodiment 2
Fig. 5 is the pastille microemulsion particle size distribution figure of the even method preparation of the ultrasonic breast of microemulsion containing matrine among the embodiment 3
Fig. 6 is the pastille microemulsion particle size distribution figure of microemulsion containing matrine high pressure homogenization method preparation among the embodiment 3.
Particle diameter unit is a nanometer among the figure.
The specific embodiment:
Prescription and proportioning:
Matrine 1g isopropyl myristate 6g
Tween 80 5g deionized water 34g
Phosphatidase 14 g makes pastille microemulsion 50g
Preparation method is:
1, high pressure homogenization method, mix deionized water and Tween 80 and be (I) mutually, mix isopropyl myristate and phospholipid and be (II) mutually, matrine is added to (II) mutually in for the pastille inner phase, under lasting the stirring pastille inner phase being mixed mutually with (I), is that a step valve pressure is 6 * 10 with mixture at processing condition
6Pa-7 * 10
6Pa (60-70bar), secondary valve pressure are 6 * 10
7Pa-7 * 10
7Under the Pa (600-700bar), homogenizing 3-5 time, the pastille microemulsion, adopt dynamic light scattering method to detect to the pastille particle size distribution of Radix Sophorae Flavescentis microemulsion, the results are shown in Figure 1, the microemulsion particle size range about 100nm (90-110nm), size is even, outward appearance is clear and bright.
2, the even method of ultrasonic breast, mix deionized water and Tween 80 and be (I) mutually, mix isopropyl myristate and phospholipid and be (II) mutually, matrine is added to (II) mutually in for the pastille inner phase, under lasting the stirring, the pastille inner phase is mixed mutually with (I), with mixture under the power of 250w, ultrasonic breast is spared 30min, get the pastille microemulsion, pastille particle size distribution to the Radix Sophorae Flavescentis microemulsion adopts dynamic light scattering method to detect, the results are shown in Figure 2, the microemulsion particle size range about 100nm (90-110nm), size is even, outward appearance is clear and bright.
Embodiment 2 preparation microemulsion containing matrines
Prescription and proportioning:
Matrine 2g oleic acid 12g
Polysorbas20 6g deionized water 50g
Caprylic/capric polyethyleneglycol glyceride 10g makes pastille microemulsion 80g
Preparation method is:
1, manual dripping method, mix deionized water and polysorbas20 and be (I) mutually, mix caprylic/capric polyethyleneglycol glyceride and oleic acid and be (II) mutually, matrine is added to (II) mutually in for the pastille inner phase, under 40 ℃ continue to be stirred with the speed of 1ml/min the pastille inner phase is dropwise added (I) mutually in, form clear and bright pastille microemulsion, pastille particle size distribution to the Radix Sophorae Flavescentis microemulsion adopts dynamic light scattering method to detect, the results are shown in Figure 3, the microemulsion particle size range about 100nm (90-110nm), size is even, outward appearance is clear and bright.
2, the even method of ultrasonic breast, mix deionized water and polysorbas20 and be (I) mutually, miscible caprylic/capric polyethyleneglycol glyceride and oleic acid be (II) mutually, matrine is added to (II) mutually in for the pastille inner phase, under lasting the stirring, the pastille inner phase is mixed mutually with (I), with mixture under the power of 250w, ultrasonic breast is spared 30min, get the pastille microemulsion, pastille particle size distribution to the Radix Sophorae Flavescentis microemulsion adopts dynamic light scattering method to detect, the results are shown in Figure 4, the microemulsion particle size range about 100nm (90-110nm), size is even, outward appearance is clear and bright.
Embodiment 3 preparation microemulsion containing matrines
Prescription and proportioning:
Matrine 4g ethyl acetate 15g
Tween 80 10g deionized water 55g
Phosphatidase 16 g makes pastille microemulsion 100g
Preparation method is:
1, the even method of ultrasonic breast, mix deionized water and Tween 80 and be (I) mutually, miscible ethyl acetate and phospholipid be (II) mutually, matrine is added to (II) mutually in for the pastille inner phase, continuing under the stirring pastille inner phase and (I) miscible, with the even 30min of mixture ultrasonic breast under the power of 250w, get the pastille microemulsion, pastille particle size distribution to the Radix Sophorae Flavescentis microemulsion adopts dynamic light scattering method to detect, the results are shown in Figure 5, the microemulsion particle size range about 100nm (90-110nm), size is even, outward appearance is clear and bright.
2, high pressure homogenization method, mix deionized water and Tween 80 and be (I) mutually, mix ethyl acetate and phospholipid and be (II) mutually, matrine being added to (II) is the pastille inner phase in mutually, under lasting the stirring pastille inner phase being mixed mutually with (I), is that a step valve pressure is 6 * 10 with mixture at processing condition
6Pa-7 * 10
6Pa (60-70bar), secondary valve pressure are 6 * 10
7Pa-7 * 10
7Under the Pa (600-700bar), homogenizing 3-5 time, the pastille microemulsion, adopt dynamic light scattering method to detect to the pastille particle size distribution of Radix Sophorae Flavescentis microemulsion, the results are shown in Figure 6, the microemulsion particle size range about 100nm (90-110nm), size is even, outward appearance is clear and bright.
The invention provides a kind of administration novel form-----microemulsion containing matrine and preparation method thereof.Overcome the existing dosage form of matrine and had shortcomings such as bioavailability is lower, less stable.The present invention is principal agent with the matrine, add different adjuvants and make microemulsion, drug administration by injection can improve target organ and tissue drug level, avoid haemolysis effect, prolong drug action time in system; Oral administration can overcome short, shortcoming such as administration number of times is frequent, bioavailability is low of half-life; Percutaneous dosing can improve the barrier function of skin, improves the skin transmitance of transdermal drug, for the clinical practice of matrine provides a kind of new form of administration.
Claims (4)
1. a microemulsion containing matrine is become to be grouped in interior each by matrine, emulsifying agent, co-emulsifier, oil phase and water, it is characterized in that described oil phase is selected from olive oil, single glyceryl linoleate, ethyl acetate, oleic acid, isopropyl myristate; Emulsifying agent is selected from soybean phospholipid, caprylic/capric polyethyleneglycol glyceride; Co-emulsifier is selected from Tween 80, polysorbas20, ethanol; Water is a deionized water; Its prescription ratio is: matrine 1-5% (g/g), emulsifying agent 4-15% (g/g), co-emulsifier 6-16% (g/g), oil phase 6-15% (g/g), water 50-70% (g/g); The microemulsion containing matrine particle size range is 90-110nm.
2. a microemulsion containing matrine is become to be grouped in interior each by matrine, emulsifying agent, co-emulsifier, oil phase and water, it is characterized in that described oil phase is an isopropyl myristate; Emulsifying agent is a phospholipid; Co-emulsifier is a Tween 80; Water is a deionized water; Its prescription is as follows:
Matrine 1g, isopropyl myristate 6g, phosphatidase 14 g, Tween 80 5g, deionized water 34g make microemulsion containing matrine 50g, and the microemulsion containing matrine particle size range is 90-110nm.
3. by the preparation method of the described microemulsion containing matrine of claim 1, it is characterized in that adopting following steps:
(1) press recipe quantity mixing deionized water and co-emulsifier for (I) mutually,
(2) mix oil phase and emulsifying agent be (II) mutually,
(3) matrine is added to (II) mutually in for the pastille inner phase,
(4) adopt manual dripping method, under 40 ℃ continue to be stirred with the speed of 1ml/min the pastille inner phase is dropwise added (I) mutually in, form clear and bright pastille microemulsion;
Or the even method of ultrasonic breast, under lasting the stirring, the pastille inner phase is mixed mutually with (I), under the power of 250w, ultrasonic breast is spared 30min with mixture, gets the pastille microemulsion;
Or the even method of high pressure homogenize breast, under lasting the stirring, the pastille inner phase is mixed mutually with (I), be 6 * 10 with mixture at a step valve
6Pa-7 * 10
6Pa, secondary valve pressure are 6 * 10
7Pa-7 * 10
7Under the Pa, even 3-5 time of homogenized milk gets the pastille microemulsion.
4. the application of the described microemulsion containing matrine of claim 1 in preparation various matrine injection types, peroral dosage form and percutaneous dosing dosage form.
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| CN200710036208A CN100998592B (en) | 2007-01-04 | 2007-01-04 | Microemulsion containing matrine |
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| CN200710036208A CN100998592B (en) | 2007-01-04 | 2007-01-04 | Microemulsion containing matrine |
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| CN101548679B (en) * | 2009-05-12 | 2014-04-02 | 沈阳药科大学 | Matrine type alkaloid microemulsion and preparation method thereof |
| CN102805726A (en) * | 2012-03-29 | 2012-12-05 | 中国人民解放军第二军医大学 | siRNA (small interfering ribose nucleic acid) micro emulsion carrier and preparation method of siRNA micro emulsion carrier |
| CN102961751A (en) * | 2012-12-21 | 2013-03-13 | 贵州省中国科学院天然产物化学重点实验室 | Composition for improving oral bioavailability of alkaloid and preparation method |
| CN103432012B (en) * | 2013-09-09 | 2015-06-24 | 北京振东光明药物研究院有限公司 | Sophocarpidine micro emulsion as well as preparation method thereof and application of micro emulsion in liquid soap |
| CN108324687B (en) * | 2018-03-29 | 2020-04-07 | 安徽医科大学 | Teriflunomide microemulsion, preparation method and application |
| CN114404366B (en) * | 2022-02-17 | 2023-12-15 | 深圳玉莱漫生物科技有限公司 | Matrine transdermal absorption nano microemulsion |
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