CN101637463A - Method for preparing borneol-modified galanthamine soft liposome cataplasm - Google Patents
Method for preparing borneol-modified galanthamine soft liposome cataplasm Download PDFInfo
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- CN101637463A CN101637463A CN200910027879A CN200910027879A CN101637463A CN 101637463 A CN101637463 A CN 101637463A CN 200910027879 A CN200910027879 A CN 200910027879A CN 200910027879 A CN200910027879 A CN 200910027879A CN 101637463 A CN101637463 A CN 101637463A
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- liposome
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Abstract
The invention relates to a method for preparing borneol-modified galanthamine soft liposome cataplasm, which relates to the preparation method of soft liposome and cataplasm which is a carrier of thesoft liposome. The borneol-modified galanthamine soft liposome cataplasm is a novel external medicinal preparation and solves the problems that long-time medicine-taking leads to adverse gastrointestinal reaction and hepatorenal damage so that no more medicine taking can be continued and senile dementia sufferers have inconvenience in medicine taking. The borneol-modified galanthamine soft liposome cataplasm is mainly used for treating senile dementia and schizophrenia. Borneol-modified galanthamine soft liposome, through the addition of borneol, promotes medicine to permeate a hemato encephalic barrier so as to improve the medicine effect. The soft liposome cataplasm prepared from the borneol-modified galanthamine soft liposome can improve the transdermal speed and the use convenience ofthe medicine and achieve the effect of slow release. In the formula of the borneol-modified galanthamine soft liposome, lycopene is added as natural antioxygen so as to improve the liposome stability.By means of secondary internal water phase addition, the preparation process improves water-soluble medicine encapsulation rate and water-soluble medicine load of the liposome.
Description
Technical field
The present invention relates to a kind of borneol-modified galanthamine soft liposome and the preparation method of its carrier cataplasma, belong to the novel external preparation of medicine.
Background technology
Have data to show, the middle of this century can reach about 400,000,000, and China will become the maximum country of the aged in the world, causes Alzheimer (AD) patient sharply to increase thus; Most Alzheimer (AD) patients are because memory weakens, intelligence reduces and usually forgets and take medicine, or take medicine more and eat wrong medicine, this causes the reduction and the toxic increase of curative effect of medication to a certain extent, and the research and development of efficient Percutaneously administrable preparation that therefore are used for Alzheimer (AD) are imperative, very urgent.Acetylcholinesteraseinhibitors inhibitors class medicine galantamine is in leading position on Alzheimer (AD) pharmaceutical market at present, have the cholinesterase activity of inhibition and regulate the active dual function of nAChR (nAChR), be used for Alzheimer (AD), schizoid treatment more; Recent studies on finds that this medicine also can suppress potassium-channel, activates dopamine receptor, can be by suppressing protection axoneurons such as after-hyperpolarization, intervention metabolism.It does not have liver toxicity, clinical practice is safer, but prolonged application be prone to untoward reaction such as its gastrointestinal tract as feel sick, vomiting, cause the part patient can't continuous use, also hindered the further popularization of galantamine clinical practice, so the Research Significance of galantamine Percutaneously administrable preparation is great.
Chinese medicine aromatic and inducing resuscitation medicine have be good at walking to scurry, the multiple god's of the refreshment of having one's ideas straightened out, refreshment effect; the disease of closing that is used for thinking is hindered, clear key is covered obnubilation, this is that cerebral cortex choline acetyl group shifts and damagedly causes that the understanding of memory and learning disorder is exactly the same with modern medicine for Alzheimer (AD) major lesions position.The present invention is according to the theory of " monarch ", the Borneolum Syntheticum of galantamine and the refreshment of Chinese medicine causing resuscitation with aromatic drugs is carried out compatibility forms " monarch makes medicine ", with Borneolum Syntheticum " assistant makes " medicine as galantamine, reach " leading group medicine " through disease effect.Modern study shows that Borneolum Syntheticum itself has the effect that the promotion medicine sees through skin and blood brain barrier, to improve the curative effect of galantamine treatment senile dementia.
Flexible lipidosome is meant adding softening agent in the bilayer of liposome and makes liposome have superior flexibility, compare envelop rate height, transdermal performance height, good stability with conventional liposome, facilitate penetration of skin and mucosa, can significantly promote the Transdermal absorption of medicine.Tradition Percutaneously administrable preparation such as rubber cream, black plaster, patch etc. easily cause serious adverse reactions such as skin allergy, stimulation.And novel hydrogels type cataplasma by water-soluble high-molecular material be prepared from have the drug loading height, water content is big, adhesion good, reusable and with the advantages such as good biocompatibility of skin, water content means that greatly the cataplasma free volume is big, diffusional resistance is little, is an important development direction of Percutaneously administrable preparation therefore.
Summary of the invention
The object of the present invention is to provide a kind of novel external preparation that is used for the treatment of senile dementia is a kind of preparation method of borneol-modified galanthamine soft liposome cataplasm.The present invention becomes flexible lipidosome with the acetylcholinesteraseinhibitors inhibitors galantamine with saturating blood brain barrier, Percutaneous absorption enhancer Borneolum Syntheticum combined preparation, wherein Borneolum Syntheticum be encapsulated in liposome in bilayer and galantamine is encapsulated in aqueous phase in the liposome, be that preparing carriers becomes Percutaneously administrable preparation then with the cataplasma.
Above-mentioned borneol-modified its medicine of galanthamine soft liposome cataplasm consists of galantamine 0.15%～0.25%, and Borneolum Syntheticum 0.1～0.2% is formed.
Above-mentioned borneol-modified galanthamine soft liposome consist of soybean lecithin 2%～5%, cholesterol 0.02～0.05%%, propylene glycol 15%～30%, galantamine 0.6%, Borneolum Syntheticum 0.3%, lycopene 0.08%, water adds to 100%.Wherein soybean lecithin and cholesterol are the liposome membrane material, and propylene glycol is a softening agent, and lycopene is an antioxidant, and galantamine is a therapeutic component, and Borneolum Syntheticum is a blood brain screen absorption enhancer.The preparation technology of above-mentioned borneol-modified galanthamine soft liposome be film materials such as the fabaceous lecithin that takes by weighing recipe quantity, cholesterol, Borneolum Syntheticum, lycopene with an amount of anhydrous alcohol solution after, shift being transported in the eggplant-shape bottle; In 55 ℃ of water-baths decompression (0.05MPa) ethanol is removed in evaporation, treat that dehydrated alcohol is taken out to the greatest extent after, continue rotation 5～10min, obtain the lipid dry film.The propylene glycol of recipe quantity is joined in the water of recipe quantity, and mix homogeneously obtains mixed liquor; Take out about 1/3 mixed liquor (residual mixed liquor is standby) galantamine of recipe quantity is dissolved in wherein, stir, obtain interior water, and place 55 ℃ of water-bath preheatings.The interior water of preheating is slowly joined in the lipid dry film, continue rotation and carry out hydration 60min; Again with its even at a high speed matter 15min; Leave standstill 15min, the microporous filter membrane circulation by 0.22um 3 times obtains dense flexible lipidosome suspension.Remaining mixed liquor is slowly added in the dense flexible lipidosome suspension, slowly stir, promptly; 4 ℃ of storages, standby.
Above-mentioned borneol-modified galanthamine soft liposome cataplasm consist of in the part and sodium polyacrylate NP-700 3%～5%, the neutral sodium polyacrylate NP-800 0.5%～1.5% of part, glycerol 25%～45%, tartaric acid 0.15～0.5%, dihydroxyaluminum aminoacetate 0.15～0.5%, ethyl hydroxybenzoate and propylparaben mixture (1: 1, w/w) 0.15～0.25%, Kaolin 2%～5%, borneol-modified galanthamine soft liposome 30%～45%, water adds to 100%.
The preparation technology of above-mentioned borneol-modified galanthamine soft liposome cataplasm is compositions such as the NP-700, the NP-800 that take by weighing recipe quantity, dihydroxyaluminum aminoacetate, Kaolin, with its mix homogeneously, join in the glycerol of recipe quantity, stirring obtains glycerol phase (A phase) again; The tartaric acid that takes by weighing recipe quantity is soluble in water, obtains water (B phase); Then with B mutually disposable join A mutually in, slow stirring at low speed 5～10min; The borneol-modified galanthamine soft liposome that adds recipe quantity again, slow stirring at low speed 5～10min again obtains the standby mastic of borneol-modified galanthamine soft liposome cataplasm.Then standby mastic is coated on the medical adhesive-bonded fabric,, packing etc. crosslinked through cutting, cut, placing is prepared from cataplasma of the present invention.
The invention has the advantages that galantamine and saturating blood brain barrier absorption enhancer Borneolum Syntheticum use in conjunction, join in the water soluble polymer framework material with the form of flexible lipidosome and to be prepared into cataplasma, its stickiness good, not residual and with the good biocompatibility of skin, do not stimulate, not irritated, easy to use, drug release time is long.
The specific embodiment
Embodiment 1: borneol-modified galanthamine soft liposome preparation
1. take by weighing fabaceous lecithin 3.0g, cholesterol 0.2g, Borneolum Syntheticum 0.3g, lycopene 0.08g, add the complete back transfer of 20ml anhydrous alcohol solution and be transported in the eggplant-shape bottle.
2. in 55 ℃ of water-baths decompression (0.05MPa) ethanol is removed in evaporation, treat that dehydrated alcohol is taken out to the greatest extent after, continue rotation 8min, obtain the lipid dry film.
3. take by weighing the 20g propylene glycol and add in the 75.9g water, mix homogeneously obtains mixed liquor; Take out 30g mixed liquor (remaining 45.9g mixed liquor is standby) the 0.6g galantamine is dissolved in wherein, stir, obtain interior water, and place 55 ℃ of water-bath preheatings.
4. the interior water with preheating slowly adds in the eggplant-shape bottle that forms the lipid dry film, after interior water adds, continues rotation in 55 ℃ and carries out hydration 60min, obtains the lipid suspension.
5. again with lipid suspension high speed homogenizer, 15000 rev/mins, spare matter 15min; Leave standstill 15min, the microporous filter membrane circulation by 0.22um 3 times obtains dense flexible lipidosome suspension; Remaining 45.9g mixed liquor is slowly added in the dense flexible lipidosome suspension, slowly stir, promptly; 4 ℃ of storages, standby.
Embodiment 2: flexible lipidosome prepares the preparation of cataplasma
1. take by weighing NP-700 3.5g, NP-800 0.6g, ethyl hydroxybenzoate and propylparaben mixture 0.2g, dihydroxyaluminum aminoacetate 0.2g, Kaolin 2.5g are with its abundant mix homogeneously; Join in the glycerol of 35g, stirring obtains glycerol phase (A phase) again.
2. take by weighing tartaric acid 0.2g, join in the 18g water, stirring obtains water (B phase).
3. with B mutually disposable join A mutually in, slowly stirring at low speed 5～10min obtains heavy-gravity mastic.
5. take by weighing the borneol-modified galanthamine soft liposome of 40g, in the mastic in joining 3. more slowly the stirring at low speed refining close 10min, obtain the standby mastic of borneol-modified galanthamine soft liposome cataplasm.
6. then with the thickness of standby mastic, evenly coat on the medical adhesive-bonded fabric, cover sealing coat with 1.5mm; Cut into the analgesic ointment of 7.0cm * 8.0cm, place 24h and make mastic full cross-linked under the purification condition of 35 ℃ of temperature, humidity 55%, packing forms cataplasma of the present invention then.
Examining report to borneol-modified galanthamine soft liposome cataplasm is as follows
1. borneol-modified galanthamine soft liposome:
Particle diameter is 200～300nm, and surface potential is-56.6mv, is 92.1% to the envelop rate of galantamine.
2. soft liposome cataplasm:
According to 2005 editions " regulations of Chinese pharmacopoeia (an appendix II emplastrum).
1. outward appearance: its creme coating of analgesic ointment of the present invention evenly, the cream face should be bright and clean, the color and luster unanimity does not have and takes off the cream phenomenon; The cleaning of backing face, nothing are leaked cream.
2. paste containing amount: paste containing amount is 〉=7.5g/100cm
2
3. inborn nature: do not have the trickling phenomenon.
4. adhesion: first viscous force is for sticking steel ball No. 18.Hold viscous force was not subjected to displacement for the 200g counterweight hangs in 2 hours.
5. weight differential :≤± 5%.
6. zest and sensitization: according to GBT16886[1] regulation of the 10th part-stimulation of .10-2005 medical apparatus and instruments biological assessment and delayed hypersensitivity test, the non-stimulated and no sensitization of borneol-modified galanthamine soft liposome cataplasm of the present invention.
3. borneol-modified galanthamine soft liposome cataplasm of the present invention shows through isolated mouse skin volume sturdy the testing of passing through inside: the borneol-modified galantamine accumulation infiltration capacity of galanthamine soft liposome in 8.0h of the present invention is 4.5 times of galantamine aqueous solutions.
Claims (5)
1. borneol-modified galanthamine soft liposome cataplasm, form by borneol-modified galanthamine soft liposome and suitable water-soluble high-molecular material, the medicine that it is characterized in that it form be by: galantamine 0.15%～0.25%, Borneolum Syntheticum 0.1～0.2% is formed.With the water-soluble high-molecular material is the main matrix material, adds borneol-modified galanthamine soft liposome, the external preparation of making through stir, crosslinked, packing is closed, is coated with, cuts, is placed in refining etc. that is used for the treatment of senile dementia.
2. borneol-modified galanthamine soft liposome according to claim 1, it is characterized in that consisting of of borneol-modified galanthamine soft liposome: soybean lecithin 2%～5%, cholesterol 0.02～0.05%%, propylene glycol 15%～30%, galantamine 0.6%, Borneolum Syntheticum 0.3%, lycopene 0.08%, water adds to 100%.Wherein soybean lecithin and cholesterol are the liposome membrane material, and propylene glycol is a softening agent, and lycopene is an antioxidant, and galantamine is a therapeutic component, and Borneolum Syntheticum is a blood brain screen absorption enhancer.
3. the preparation method of borneol-modified galanthamine soft liposome according to claim 1 is characterized in that: the film materials such as fabaceous lecithin, cholesterol, Borneolum Syntheticum, lycopene that take by weighing recipe quantity with an amount of anhydrous alcohol solution after, shift being transported in the eggplant-shape bottle; In 55 ℃ of water-baths decompression (0.05MPa) ethanol is removed in evaporation, treat that dehydrated alcohol is taken out to the greatest extent after, continue rotation 5～10min, obtain the lipid dry film.The propylene glycol of recipe quantity is joined in the water of recipe quantity, and mix homogeneously obtains mixed liquor; Take out about 1/3 mixed liquor (residual mixed liquor is standby) galantamine of recipe quantity is dissolved in wherein, stir, obtain interior water, and place 55 ℃ of water-bath preheatings.The interior water of preheating is slowly joined in the lipid dry film, continue rotation and carry out hydration 60min; Again with its even at a high speed matter 15min; Leave standstill 15min, the microporous filter membrane circulation by 0.22um 3 times obtains dense flexible lipidosome suspension.Remaining mixed liquor is slowly added in the dense flexible lipidosome suspension, slowly stir, promptly; 4 ℃ of storages, standby.
4. borneol-modified galanthamine soft liposome cataplasm according to claim 1, it is characterized in that consisting of of soft liposome cataplasm: the neutral sodium polyacrylate NP-700 3%～5% of part, the neutral sodium polyacrylate NP-8000.5% of part～1.5%, glycerol 25%～45%, tartaric acid 0.15～0.5%, dihydroxyaluminum aminoacetate 0.15～0.5%, ethyl hydroxybenzoate and propylparaben mixture (1: 1, w/w) 0.15～0.25%, Kaolin 2%～5%, borneol-modified galanthamine soft liposome 30%～45%, water adds to 100%.
5. the preparation method of borneol-modified galanthamine soft liposome cataplasm according to claim 1, it is characterized in that: its preparation technology is compositions such as the NP-700, the NP-800 that take by weighing recipe quantity, dihydroxyaluminum aminoacetate, Kaolin, with its mix homogeneously, join in the glycerol of recipe quantity, stirring obtains glycerol phase (A phase) again; The tartaric acid that takes by weighing recipe quantity is soluble in water, obtains water (B phase); Then with B mutually disposable join A mutually in, slow stirring at low speed 5～10min; The borneol-modified galanthamine soft liposome that adds recipe quantity again, slow stirring at low speed 5～10min again obtains the standby mastic of borneol-modified galanthamine soft liposome cataplasm.Then standby mastic is coated on the medical adhesive-bonded fabric,, packing etc. crosslinked through cutting, cut, placing is prepared from cataplasma of the present invention.
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| CN200910027879A CN101637463A (en) | 2009-05-18 | 2009-05-18 | Method for preparing borneol-modified galanthamine soft liposome cataplasm |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109528693A (en) * | 2018-12-20 | 2019-03-29 | 武汉科福新药有限责任公司 | A kind of rapamycin cataplasm and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109528693A (en) * | 2018-12-20 | 2019-03-29 | 武汉科福新药有限责任公司 | A kind of rapamycin cataplasm and preparation method thereof |
| CN109528693B (en) * | 2018-12-20 | 2022-03-01 | 武汉科福新药有限责任公司 | Rapamycin cataplasm and preparation method thereof |
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Open date: 20100203 |