CN1605356A - Preparation process and prescription of oleum fructus bruceae containing microemulsion - Google Patents

Preparation process and prescription of oleum fructus bruceae containing microemulsion Download PDF

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Publication number
CN1605356A
CN1605356A CN 200410050814 CN200410050814A CN1605356A CN 1605356 A CN1605356 A CN 1605356A CN 200410050814 CN200410050814 CN 200410050814 CN 200410050814 A CN200410050814 A CN 200410050814A CN 1605356 A CN1605356 A CN 1605356A
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fructus bruceae
oleum fructus
microemulsion
gram
preparation
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CN 200410050814
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CN100508954C (en
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李校堃
姚崇舜
蔺胜照
项琪
李宏
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Guangzhou Jin Yang cosmetics company limited
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Medical And Biological Technology Research And Development Center Jinan Univ G
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Abstract

The present invention discloses micro emulsion preparation containing brucea fruit oil and its preparation process. The micro emulsion preparation contains brucea fruit oil as main pharmacological component as well as emulsifier, emulsification assistant and vegetable oil; and may be micro emulsion, sub-nano emulsion, powder for injection, ointment, gel, or solid liposome nanometer particle. It is administrated via intravenous injection, oral taking, transdermal massage, spraying, rectum administration, etc. Compared with common emulsion, the present invention has the features of small particle size, high thermal stability, low toxicity, high bioavailability, etc.

Description

A kind of preparation technology and prescription that contains the Oleum Fructus Bruceae microemulsion
Technical field:
The present invention relates to a kind of preparation technology and prescription of Oleum Fructus Bruceae microemulsion.
It can be prepared into Emulsion, injectable powder, unguentum, cream, solid lipid nanoparticle, and route of administration is intravenous injection, oral, skin massaging, spraying and rectally etc.
Background information:
Cancer is an ancient disease, has become the main killer of health of people in 21st century, as if especially in some economically developed countries, cancer can not reduce along with expanding economy.World Health Organization (WHO) estimates, every year on average dead malignant tumor person reaches 6,900,000 people in the whole world more than 50 hundred million populations, and the neopathy rate is about 8,700,000 examples, and wherein nearly 60% dies from pulmonary carcinoma, gastric cancer, breast carcinoma, colorectal carcinoma, oral cancer, hepatocarcinoma, cervical cancer, and the esophageal carcinoma are to be only second to the second largest cause of the death that cardiovascular shoots dead.Based on such reality, national governments, research institution and drugmaker are paid much attention to and huge investment pharmaceutical research and antitumor drug exploitation for a long time always, thereby make oncotherapy constantly developed.The screening antitumor drug is an approach that gets twice the result with half the effort in Chinese herbal medicine.
Fructus Bruceae is the seed of quassia Fructus Bruceae, and flavor is extremely bitter, cold in nature, poisonous, and being used for treating the feeling of stuffiness in chest expires miasma etc.Existing Java brucea fruit oil emulsion injection is mainly used in treatment pulmonary carcinoma, digestive tract tumor clinically, and main active is an oleic acid.Disclosed bibliographical information shows that the main adverse reaction of Java brucea fruit oil emulsion injection has: feel sick, anorexia, vomiting, heart rate and accelerated breathing, cyanosis, severe patient can cause arrhythmia and death.Aspect pharmacy, common Emulsion belongs to thermodynamic unstable system, easily produces the profit lamination in storage process, and less stable has limited the clinical expansion of this product.By institute of materia medica, the Chinese Academy of Sciences Shanghai tumor seminar result of study of Fructus Bruceae was shown in 1998 to 1999, the Fructus Bruceae breast has very strong inhibitory action to topological structure enzyme II, with ADM, and DDP, MMC, medicines such as 5-Fu are collaborative can to play tumor-inhibiting action once more to drug-fast tumor cell line.This has very important significance for tumor treatment.
Summary of the invention:
The object of the present invention is to provide a kind of preparation technology and prescription of the microemulsion of making by natural drug extract Oleum Fructus Bruceae.Oleum Fructus Bruceae is through CO 2Supercritical extraction and getting, its extraction is apparent to those skilled in the art, also can obtain from commercial channels.The pharmaceutical composition that comprises the Oleum Fructus Bruceae microemulsion provided by the invention, comprise that microemulsion, inferior nano-emulsion, injectable powder, unguentum, gel, solid lipid nanoparticle have the antineoplastic function, route of administration is intravenous injection, oral, skin massaging, spraying and rectally etc., and the preparation method of a kind of microemulsion, inferior nano-emulsion, injectable powder, unguentum, gel, solid lipid nanoparticle is provided.The particle diameter of microemulsion should be below 0.8 micron, but the optimal granularity scope is controlled at below 500 nanometers.Intravenously administrable is controlled at below 200 nanometers with the particle diameter of preparation, and the optimum grain-diameter scope should be about 100 nanometers.It is to be main pharmaceutical component with Oleum Fructus Bruceae, and containing microemulsion, sub-nanometer emulsion, injectable powder, unguentum, gel, the solid lipid nanoparticle of emulsifying agent, co-emulsifier, vegetable oil preparation, route of administration is intravenous injection, oral, skin massaging, spraying and rectally etc.This microemulsion formulation particle diameter is little, and scope is below 800 nanometers, and solution is clear and bright, Thermodynamically stable.
In one embodiment of the invention, a kind of Oleum Fructus Bruceae microemulsion and preparation technology thereof are provided, wherein said microemulsion is main pharmaceutical component with Oleum Fructus Bruceae, and containing Emulsion, injectable powder, gel, the solid lipid nano ball that emulsifying agent, co-emulsifier, vegetable oil make, route of administration can be intravenous injection, oral, skin massaging, spraying and rectally etc.
Said emulsifying agent can be selected from surfactant-based, the sugar fatty acid esters of for example phospholipid, triglyceride, Tween 80, polysorbas20, polyxyethylated esters, amine N-oxidation.
Said co-emulsifier for example can be selected from medium chain alcohols such as ethanol, n-butyl alcohol, hot tricaprin.
Said vegetable oil can be selected from for example refined soybean oil, olive oil, Oleum Helianthi, castor oil hydrogenated, capric acid and Palmic acid.
In one embodiment of the invention, said Oleum Fructus Bruceae microemulsion is characterised in that: contain Oleum Fructus Bruceae 5-20 gram in per 100 milliliters of emulsions, and refining fabaceous lecithin 0.5-15 gram, propylene glycol 1-10 milliliter, the particle size range of emulsion droplet is below 800 nanometers.
In another embodiment of the invention, said Oleum Fructus Bruceae microemulsion is characterised in that: can also add glycerol in said above-mentioned Emulsion, poloxamer is prepared into microemulsion, it consists of and contains Oleum Fructus Bruceae 0.5-15 gram in per 100 milliliters of emulsions, refining fabaceous lecithin 0.5-1.5 gram, glycerol 2.0-5.0 gram, poloxamer 188 0.8-3.2 gram, all the other are water for injection, its particle size range is below 300 nanometers.Route of administration is intravenous injection.
In another embodiment of the invention, this Emulsion is prepared to injectable powder, and it consists of Oleum Fructus Bruceae 0.5-15 gram, polyvinyl alcohol K30.
In another scheme of the present invention, being characterized as it and being prepared to gel of said Oleum Fructus Bruceae microemulsion, it consists of Oleum Fructus Bruceae 1-30 gram, fabaceous lecithin 0.5-3.0 gram, card pool nurse 941 10-30 gram, triethanolamine 13.5-40.5 gram.
In another scheme of the present invention, said Oleum Fructus Bruceae microemulsion is characterised in that: add stearic acid in said Emulsion it is prepared into solid lipid nanoparticle, it consists of Oleum Fructus Bruceae 1-15 gram, exquisite fabaceous lecithin 0.5-1.0 gram, glycerol 2.0-5.0 gram, poloxamer 188 0.6-3.0 gram, stearic acid 10-30 gram.
Another program of the present invention also provides the method for preparing above-mentioned Oleum Fructus Bruceae microemulsion, it is characterized in that: contained Oleum Fructus Bruceae all adopts CO in injectable emulsion, injectable powder and the gel 2The supercritical extraction technology, and it is made with extra care, make it reach the standard of oil for injection.
In preparation method of the present invention, being characterized as of a kind of preferred manufacturing procedure: the preparation method of preparation microemulsion may further comprise the steps: (1) is with glycerol, the Oleum Fructus Bruceae mixing of recipe quantity; (2) add ethanol and dissolve in right amount, get clear solution; (3) add the recipe quantity fabaceous lecithin, 80 ℃ of waters bath with thermostatic control dissolve settled solution; (4) add equal-volume water for injection, mixing, packing.
In one embodiment of the invention, this preparation method is characterised in that: the preparation method of preparation Oleum Fructus Bruceae injectable powder is: getting an amount of polyvinyl alcohol K30 with the Oleum Fructus Bruceae enclose, be scattered in lyophilization in the glucose solution, is proppant with mannitol.
Still in one embodiment of the invention, the method is characterized in that: the preparation method of Oleum Fructus Bruceae solid lipid nano ball is: get recipe quantity Oleum Fructus Bruceae, fabaceous lecithin and stearic acid, under logical condition of nitrogen gas, be heated to 80 ℃ ± 5 ℃, stir the glycerol and the poloxamer 188 that add uniform temp down and make colostrum, under 80 ℃ ± 5 ℃ and the logical nitrogen condition, even 5 times of high pressure dispersing emulsification machine breast fills the nitrogen packing, and cooling forms the Oleum Fructus Bruceae suspension rapidly.
The microemulsion emulsion droplet particle diameter of the present invention preparation is below 800nm, and Thermodynamically stable can improve or improve the dissolubility and the biological effectiveness of Fructus Bruceae breast.The present invention can reduce Oleum Fructus Bruceae dosage, improves effectiveness, the targeting of preparation, and reducing stimulates gastrointestinal.Production technology is simple, does not need special instrument and equipment, helps industrialized great production.
Now the following examples are further detailed the present invention, but these embodiment want in office where face limits the invention.
Embodiment:
Embodiment 1 (microemulsion): get 20 gram glycerol, 80 gram Oleum Fructus Bruceae and hot tricaprin 10 gram mixings, stirring makes molten, adds an amount of clear solution that gets of ethanol; Add 15 gram fabaceous lecithins again, 80 ℃ of waters bath with thermostatic control dissolve settled solution; Add equal-volume water for injection, mixing fills nitrogen, packing.Sterilized 45 minutes down for 105 ℃.
Embodiment 2 (inferior nano-emulsion): 100 gram medium chain triglycerides, 12 gram injection fabaceous lecithins, 22 gram glycerol for injection and an amount of water for injection are placed high-speed tissue mashing machine, under nitrogen current, disperse, two dispersing emulsification machines of impouring again, refined soybean oil 50 grams and the Oleum Fructus Bruceae 50 that slowly add 90 ℃ restrain, under nitrogen current emulsifying to the emulsion droplet particle diameter less than 0.8 μ m after, add water to 1000 milliliters, filter, fill, fill nitrogen, gland, autoclaving (115 ℃, 25 minutes) promptly.Store (avoiding freezing) below 25 ℃.
Embodiment 3 (solid lipid nanoparticle): get 50 gram Oleum Fructus Bruceae, 10 gram fabaceous lecithins and 30 gram stearic acid, under logical condition of nitrogen gas, be heated to 80 ℃ ± 5 ℃, stir and to add uniform temp down and contain the solution that glycerol 30 grams and poloxamer 188 5 restrain and make colostrum, under 80 ℃ ± 5 ℃ and the logical nitrogen condition, even 5 times of high pressure dispersing emulsification machine breast, fill the nitrogen packing, cooling forms the Oleum Fructus Bruceae suspension rapidly.
Embodiment 4 (gel): Oleum Fructus Bruceae 30 grams, 80 ℃ ± 5 ℃ heating in water bath to fabaceous lecithins of fabaceous lecithin 0.5-3.0 gram dissolve fully, add card pool nurse 941 30 grams, and triethanolamine 40.5 grams are promptly.
Embodiment 5 (injectable powder): get 50 gram polyvinyl alcohol K30 with Oleum Fructus Bruceae 5 gram enclose, be scattered in 500 milliliters of the glucose solutions, lyophilization is a proppant with mannitol.

Claims (15)

1, a kind of Oleum Fructus Bruceae microemulsion is characterized in that, said microemulsion is main pharmaceutical component with Oleum Fructus Bruceae, and contains emulsifying agent, co-emulsifier, vegetable oil.
2, Oleum Fructus Bruceae microemulsion as claimed in claim 1, wherein said emulsifying agent are surfactant-based, the sugar fatty acid esters of phospholipid, triglyceride, Tween 80, polysorbas20, polyxyethylated esters, amine N-oxidation.
3, Oleum Fructus Bruceae microemulsion as claimed in claim 1, wherein said co-emulsifier are medium chain alcohols such as ethanol, n-butyl alcohol, hot tricaprin.
4, Oleum Fructus Bruceae microemulsion as claimed in claim 1, wherein said vegetable oil is refined soybean oil, olive oil, castor oil hydrogenated, Oleum Helianthi, capric acid and Palmic acid.
5, a kind of pharmaceutical composition that comprises Oleum Fructus Bruceae microemulsion as claimed in claim 1 is characterized by it and can be injectable powder, gel or solid lipid nano ball.
6, compositions as claimed in claim 5 is characterized by it and can be the form of intravenously administrable, oral administration or percutaneous dosing.
7, the drug regimen of a kind of Oleum Fructus Bruceae microemulsion as claimed in claim 5 is characterized in that: contain Oleum Fructus Bruceae 5-20 gram in per 100 milliliters of emulsions, and refining fabaceous lecithin 0.5-15 gram, propylene glycol 1-10 milliliter, the particle size range of emulsion droplet is below 800 nanometers.
8, the drug regimen of a kind of Oleum Fructus Bruceae microemulsion as claimed in claim 5, it is characterized in that: above-mentioned Emulsion can also add glycerol, poloxamer is prepared into microemulsion, it consists of and contains Oleum Fructus Bruceae 0.5-15 gram in per 100 milliliters of emulsions, exquisite fabaceous lecithin 0.5-1.0 gram, glycerol 2.0-5.0 gram, poloxamer 188 0.8-3.2 gram, all the other are water for injection, its particle size range is below 300 nanometers.Route of administration is intravenous injection.
9, the drug regimen of a kind of Oleum Fructus Bruceae microemulsion as claimed in claim 5 is characterized in that: above-mentioned Emulsion can also be prepared into injectable powder, and it consists of Oleum Fructus Bruceae 0.5-15 gram, polyvinyl alcohol k30.
10, the drug regimen of a kind of Oleum Fructus Bruceae microemulsion as claimed in claim 5, it is characterized in that: above-mentioned Emulsion can also be prepared into gel, and it consists of Oleum Fructus Bruceae 1-30 gram, fabaceous lecithin 0.5-3.0 gram, card pool nurse 941 10-30 gram, triethanolamine 13.5-40.5 gram.
11, the drug regimen of a kind of Oleum Fructus Bruceae microemulsion as claimed in claim 5, it is characterized in that: above-mentioned Emulsion can also add stearic acid and be prepared into solid lipid nanoparticle, it consists of Oleum Fructus Bruceae 1-15 gram, exquisite fabaceous lecithin 0.5-1.0 gram, glycerol 2.0-5.0 gram, poloxamer 188 0.6-3.0 gram, stearic acid 10-30 gram.
12, a kind of preparation technology who prepares Oleum Fructus Bruceae microemulsion as claimed in claim 1, it is characterized in that: contained Oleum Fructus Bruceae all adopts CO in injectable emulsion, injectable powder and the gel 2The supercritical extraction technology, and it is made with extra care, make it reach the standard of oil for injection.
13, the preparation technology of preparation Oleum Fructus Bruceae microemulsion as claimed in claim 8 is characterized in that: the preparation method of preparation microemulsion may further comprise the steps: (1) with glycerol, the Oleum Fructus Bruceae mixing of recipe quantity; (2) add ethanol and dissolve in right amount, get clear solution; (3) add recipe quantity fabaceous lecithin, 80 ℃ of dissolved settled solutions of water bath with thermostatic control; (4) add equal-volume water for injection, mixing, packing.
14, the preparation technology of preparation Oleum Fructus Bruceae microemulsion as claimed in claim 9, it is characterized in that: the preparation method of preparation Oleum Fructus Bruceae injectable powder is: get an amount of polyvinyl alcohol K30 with the Oleum Fructus Bruceae enclose, being scattered in lyophilization in the glucose solution, is proppant with mannitol.
15, the preparation technology of preparation Oleum Fructus Bruceae microemulsion as claimed in claim 11, it is characterized in that: the preparation method of Oleum Fructus Bruceae solid lipid nano ball is: get recipe quantity Oleum Fructus Bruceae, fabaceous lecithin and stearic acid, under logical condition of nitrogen gas, be heated to 80 ℃ ± 5 ℃, the following adding of stirring uniform temp contains glycerol and poloxamer 188 makes colostrum, under 80 ℃ ± 5 ℃ and the logical nitrogen condition, even 5 times of high pressure dispersing emulsification machine breast fills the nitrogen packing, and cooling forms the Oleum Fructus Bruceae suspension rapidly.
CNB2004100508142A 2004-07-27 2004-07-27 Preparation process and prescription of oleum fructus bruceae containing microemulsion Active CN100508954C (en)

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101040847B (en) * 2006-12-18 2010-05-26 周文忠 Nanometer medicine agent produced by hydrogenated castor oil and the technique of preparing the same
CN101984808A (en) * 2010-07-22 2011-03-16 福建诺德生物科技有限责任公司 Microemulsion preparation taking rosin-based vegetable oil as solvent and preparation method thereof
CN101288682B (en) * 2008-06-06 2011-07-20 广东药学院 Microemulsion containing brucea javanica oil and preparation method thereof
EP2411032B1 (en) * 2009-03-27 2014-07-09 Evoria GmbH Plant extracts for the treatment of skin diseases
CN106309515A (en) * 2015-07-08 2017-01-11 上海中医药大学附属龙华医院 Brucea javanica oil lyotropic liquid crystal nanoparticle dispersion body, raw material composition and preparation method
CN108159120A (en) * 2018-01-17 2018-06-15 中国农业科学院兰州畜牧与兽药研究所 A kind of Chinese medicine transdermal agent and preparation method thereof
CN112220815A (en) * 2020-10-23 2021-01-15 绍兴市妇幼保健院 Brucea javanica oil emulsion and application thereof in inhibiting hepatitis B virus

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101040847B (en) * 2006-12-18 2010-05-26 周文忠 Nanometer medicine agent produced by hydrogenated castor oil and the technique of preparing the same
CN101288682B (en) * 2008-06-06 2011-07-20 广东药学院 Microemulsion containing brucea javanica oil and preparation method thereof
EP2411032B1 (en) * 2009-03-27 2014-07-09 Evoria GmbH Plant extracts for the treatment of skin diseases
CN101984808A (en) * 2010-07-22 2011-03-16 福建诺德生物科技有限责任公司 Microemulsion preparation taking rosin-based vegetable oil as solvent and preparation method thereof
CN101984808B (en) * 2010-07-22 2012-11-21 福建诺德生物科技有限责任公司 Microemulsion preparation taking rosin-based vegetable oil as solvent and preparation method thereof
CN106309515A (en) * 2015-07-08 2017-01-11 上海中医药大学附属龙华医院 Brucea javanica oil lyotropic liquid crystal nanoparticle dispersion body, raw material composition and preparation method
CN108159120A (en) * 2018-01-17 2018-06-15 中国农业科学院兰州畜牧与兽药研究所 A kind of Chinese medicine transdermal agent and preparation method thereof
CN112220815A (en) * 2020-10-23 2021-01-15 绍兴市妇幼保健院 Brucea javanica oil emulsion and application thereof in inhibiting hepatitis B virus

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