CN1868463A - Slow-release prepn. contg. alpha-lipoic acid or its derivatives, and preparing method therefor - Google Patents
Slow-release prepn. contg. alpha-lipoic acid or its derivatives, and preparing method therefor Download PDFInfo
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- CN1868463A CN1868463A CN 200610035954 CN200610035954A CN1868463A CN 1868463 A CN1868463 A CN 1868463A CN 200610035954 CN200610035954 CN 200610035954 CN 200610035954 A CN200610035954 A CN 200610035954A CN 1868463 A CN1868463 A CN 1868463A
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- lipoic acid
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Abstract
A slow-release tablet of alpha-thioctic acid or its derivative used as medicine, food additive, or cosmetic has a single slow-release layer made of hydroxypropyl methylcellulose or one slow-release layer plus one ordinary-release layer for quickly releasing the alpha-thioctic acid or its derivative. Its preparing process is also disclosed.
Description
Technical field
The invention belongs to the biological medicine technology field, relate to slow releasing preparation of alpha-lipoic acid or derivatives thereof and preparation method thereof.
Background technology
(α-lipoic acid LA) is described as " omnipotent antioxidant " to alpha-lipoic acid, is the strongest a kind of of effect in the known natural inhibitor, and its chemistry is by name 1,2-dithiolane-3-valeric acid.LA usually and the lysine residue epsilon-amino covalent bond in the protein molecule exists with the form of amido link in the animal vegetable tissue.Secondly the plant that LA content is the highest is Herba Spinaciae, is Fructus Lycopersici esculenti and Caulis et Folium Brassicae capitatae; LA content is the highest in liver and the renal tissue in animal body.LA is the cofactor of pyruvic dehydrogenase.It is a metabolic antioxidant, can be converted into the dihydrolipoic acid (DHLA) of reduced form in vivo, and molecular formula is C
8H
14S
2O
2, molecular weight is 206.33.
In recent years, LA and DHLA are subjected to (the Treat Endocrinol.2004 that shows great attention to of international biomedical sector in the important function aspect antioxidation, carbohydrate metabolism, diabetic complication and other the multiple treatment of diseases; 3 (3): 173-89; Env ToxPharmaco.2001; 10:167-172.Nutrition.2001; 17 (10): 888-895).
The biological agent of LA mainly contains:
1, antioxidation: remove free radical and active oxygen.LA can remove hydroxyl radical free radical (OH), hydrogen peroxide (H
2O
2), singlet oxygen (
1O
2), nitric oxide free radical (NO), peroxidating nitroso-group (OONO) and time green acids (HClO).Though LA can not remove peroxide radical (ROO) and superoxide radical (O
2), but therefore going back ortho states DHLA and removing other free radical beyond the singlet oxygen of LA, in LA and the DHLA mutual conversion and metabolism regenerative process in vivo, can remove above-mentioned all free radicals.DHLA is a kind of strong reductant, many oxidized form antioxidants of reducible regeneration such as ascorbic acid, vitamin E, the sweet peptide of ancient light (GSH), ubiquinone, thioredoxin etc.The oxidoreduction of LA and DHLA has activated the metabolic cycles of other antioxidant in the organism, forms unique biological antioxidant regeneration cycle net Lip river.
2, to the therapeutical effect of diabetes and chronic complicating diseases of diabetes.LA can strengthen carbohydrate metabolism (referring to Lipoic acid in healthand disease, Marcel Dekker Inc., New York 1997, p87-88), in recent years research is reconfirmed, LA can strengthen the absorption to glucose of non-insulin-dependent diabetes mellitus animals skeletal muscle and erythrocyte, and blood sugar lowering, can weaken the response to oxidative stress that diabetes produce.Hyperglycemia can cause that oxidative stress, radical damage, lipid metabolism are unusual, blood vessel injury and the low inferior apoptosis that causes neurocyte of nervous function, thereby brings out diabetic neuropathy.LA can remove free radical, the regeneration antioxidant, weaken oxidative stress, accelerate nerve conduction velocity, repair neurological handicap, make neuropeptide tyrosine, nerve growth factor and P material recover normal, thereby alleviate or eliminated the polyneuropathy symptom of diabetes effectively.But LA is prevent diabetes cataract, and prevent diabetes cardiovascular injury also.
3, other.For many years, LA is used for the treatment of the liver disorder always, and paraesthesia also can suppress (the Klin.Wochenschr..1991 that duplicates of HIV-1 virus; 69 (15): 722-724).The racemic modification of LA also has the protection cell, antiinflammatory and analgesic activity.
In sum, LA is a kind of high-efficiency antioxidant agent, has important function aspect the prevention of numerous disease and the treatment.
The alpha-lipoic acid or derivatives thereof is a kind of heat-labile compound, because present conventional conventional tablet utilizes hot cut method to melt extrude and obtains, temperature is generally at 50-200 ℃, possible thermal decomposition alpha-lipoic acid and influence its biological activity, not having as yet at present can be practical, can keep the report of slow releasing preparation development of the alpha-lipoic acid or derivatives thereof of drug effect lastingly.
Summary of the invention
The objective of the invention is, propose a kind of stable, persistent drug effect that has, can significantly improve the slow releasing preparation and preparation method thereof of alpha-lipoic acid or derivatives thereof of the therapeutic effect of alpha-lipoic acid or derivatives thereof.
Further aim of the present invention is to propose a kind of existing slow release layer part, and the double-layer sustained release tablets of the alpha-lipoic acid or derivatives thereof of often releasing layer segment is arranged again, it is reached have ordinary preparation and prove effective fast and slow releasing preparation lasting medicine, the advantage that work in coordination with two aspects of stablizing.
The technical scheme of the slow releasing preparation of alpha-lipoic acid or derivatives thereof proposed by the invention, be with the alpha-lipoic acid or derivatives thereof as principal agent, as blocker, make slow releasing tablet with hydroxypropyl emthylcellulose, its component proportioning is as follows:
Principal agent 10-1000 milligram
Starch 0-60 milligram
Lactose 0-50 milligram
Hydroxypropyl emthylcellulose 10-1000 milligram
Ethyl cellulose 0-20 milligram
Microcrystalline Cellulose 0-200 milligram
1.5% Gonak 1-40 milligram
Pulvis Talci 1-5 milligram
Magnesium stearate 1-2 milligram.
On this basis, the double-layer sustained release tablets of the alpha-lipoic acid or derivatives thereof that the present invention further proposes, be as slow release layer with described slow releasing tablet component, increase on its basis one deck with the alpha-lipoic acid or derivatives thereof be principal agent often release layer, make double-layer tablet, the described component proportioning of often releasing layer is:
Principal agent 10-1000 milligram
Starch 1-60 milligram
Lactose 1-50 milligram
Ethyl cellulose 1-20 milligram
Microcrystalline Cellulose 1-200 milligram
6% polyvinylpyrrolidonesolution solution 1-40 milligram
Pulvis Talci 1-5 milligram
Magnesium stearate 1-2 milligram.
Below be the further preferred version of technique scheme:
The content of alpha-lipoic acid or derivatives thereof principal agent in slow release layer is the 20-800 milligram.
Alpha-lipoic acid or derivatives thereof principal agent at slow release layer and the total content of often releasing in the layer be the 100-1000 milligram, be preferably the 100-600 milligram.
Alpha-lipoic acid or derivatives thereof of the present invention can be the R-(+) of racemic alpha-lipoic acid, enantiomer-pure-or (+)-dihydrolipoic acid or (-)-dihydrolipoic acid or its mixture of S-(-)-alpha-lipoic acid or its mixture, racemic dihydrolipoic acid, enantiomer-pure.
The preparation method of the slow releasing preparation of described alpha-lipoic acid or derivatives thereof is as follows:
The preparation method of monolayer slow releasing tablet is, fully mixes by described slow releasing tablet component, and carries out wet granulation, and again 5-70 ℃ of drying, with direct compression behind the dried granule granulate.
The preparation method of double-layer sustained release tablets is, respectively with slow release layer and often release the layer each component fully mix, and carry out wet granulation, make slow-releasing granules respectively and often release granule, again 5-70 ℃ of drying, behind dried granule granulate, place the administration funnel respectively often releasing granule and slow-releasing granules, be pressed into bilayer tablet with bi-layer tablet press.
The slow releasing preparation of prepared alpha-lipoic acid or derivatives thereof comprises that the slow releasing tablet of monolithic and double-layer sustained release tablets can carry out coating or coating not, and its art for coating is existing traditional handicraft.
The slow releasing preparation of alpha-lipoic acid or derivatives thereof provided by the present invention comprises the slow releasing tablet of monolithic and the application that double-layer sustained release tablets can be made medicine preparation, food additive or cosmetics.Said preparation can be by oral, and skin is parenteral, rectum, positions such as vagina are to the organism administration.
In the slow releasing preparation of alpha-lipoic acid or derivatives thereof of the present invention, because the lasting release of in slow release layer, using hydroxypropyl emthylcellulose to prolong principal agent as blocker, its principal agent composition can continue to discharge from slow release layer more than 5 hours, can make the principal agent in vivo can useful effect more than 8 hours.
The present invention has passed through the test of external release: the method that provides according to Chinese Pharmacopoeia, carry out the dissolution in vitro experiment that the present invention prepares double-layer sustained release tablets, what Fig. 1 showed is the double-layer sustained release tablets dissolution in vitro experimental result that the present invention prepares, the double-layer sustained release tablets that shows the present invention's preparation is in 1-3 hour, and the release layer medicine discharges rapidly; The slow release layer drug slow discharges in 3-8 hour, has reached the requirement of the double-layer sustained release tablets release characteristics of the present invention's design.This double-layer sustained release tablets has in vivo that ordinary preparation proves effective soon, slow releasing preparation lasting medicine, stable characteristics, can reach the often release part medicine fully discharges rapidly in vivo, after reaching effective blood drug concentration fast, slow-released part slowly discharges again, and continue to keep the effect of effective blood drug concentration stably, and just have further reduction side effect, safety good, keep long, advantage such as oral absorption is rapid of treatment time.
Description of drawings
Principal agent dissolution experimental result picture when Fig. 1 is the external release of double-layer sustained release tablets.
Among the figure, A is the rapid release curve, and B is the sustained release curve, and C is the treatment concentration curve.
The specific embodiment
Embodiment 1
Principal agent is that the prescription of the double-layer sustained release tablets of R-(+)-alpha-lipoic acid is:
Slow releasing pharmaceutical raw material components and content are:
200 milligrams of R-(+)-alpha-lipoic acid
10 milligrams of lactose
125 milligrams of hydroxypropyl emthylcelluloses
20 milligrams of ethyl celluloses
40 milligrams of 1.5% Gonaks
5 milligrams of Pulvis Talci
2 milligrams of magnesium stearate
Normal release raw material component and content are:
100 milligrams of R-(+)-alpha-lipoic acid
10 milligrams of starch
10 milligrams of 6% polyvinylpyrrolidonesolution solution
2 milligrams of Pulvis Talci
2 milligrams of magnesium stearate
The film-coat component and the content of this double-layer sustained release tablets are:
4 milligrams of hydroxypropyl emthylcelluloses
6 milligrams of PEG400s
0.5 milligram of titanium dioxide
1 milligram of Pulvis Talci
80 milliliters of food stage ethanol
20 milliliters in water
The preparation technology of this double-layer tablet is as follows:
Respectively R-(+)-alpha-lipoic acid, starch, hydroxypropyl emthylcellulose, ethyl cellulose, microcrystalline Cellulose, carboxymethyl starch sodium are pressed component of the present invention and content drying, pulverizing, crossed 100 mesh sieves respectively, standby.
The preparation technology of normal release raw material:
Respectively R-(+)-alpha-lipoic acid, starch, lactose, microcrystalline Cellulose being crossed 100 mesh sieves by content of the present invention mixes.Add 6% polyvinylpyrrolidonesolution solution and make soft material in right amount, with agglomerating, the light pressure of the holding degree of being that promptly looses; Crossing 18 eye mesh screens granulates; With 16 eye mesh screen granulate, add carboxymethyl starch sodium and lubricant, mix homogeneously is immediate-release granules.
The preparation technology of slow releasing pharmaceutical raw material:
Press component of the present invention and content with R-(+)-alpha-lipoic acid, starch, mistake 80 mesh sieve mix homogeneously.Lactose,, ethyl cellulose, microcrystalline Cellulose, hydroxypropyl emthylcellulose cross mix homogeneously behind 80 mesh sieves by content of the present invention.Again two kinds of mixture are crossed mix homogeneously behind 80 mesh sieves.Add 1.5% Gonak and make soft material in right amount, with the promptly diffusing degree of holding of being of agglomerating, light pressure; Crossing 18 eye mesh screens granulates; Drying is 2 hours under 45 ℃ of conditions; With 16 eye mesh screen granulate, add lubricant, mix homogeneously is slow-releasing granules.
Immediate-release granules and slow-releasing granules are placed the administration funnel respectively, use the bi-layer tablet press tabletting.
Film coating procedure:
The preparation of coating solution: in the ethanol with hydroxypropyl emthylcellulose adding 95%, under constantly stirring, add entry by component of the present invention and content, it is fully dissolved, add other raw materials of recipe quantity again, stirred 30-50 minute, promptly get coating solution.
Art for coating: plain sheet is removed fine powder add in the coating pan, be preheated to 30 ℃, regulate compressed air, making its pressure is 0.4Mpa, regulating the coating pan rotating speed is 3-10 rev/min, spray speed to the sheet of regulating spray gun heavily increased to 1% o'clock, stopped coating, and coated tablet is taken out from coating pan, put into the drying cupboard of desiccant, after at least 5 hours, take out check, packing promptly gets this product.
Described various components contents is the content of making 1 double-layer tablet of the present invention.
Embodiment 2
Principal agent is that the prescription of the double-layer sustained release tablets of S-(-)-alpha-lipoic acid is:
Slow releasing pharmaceutical raw material components and content are:
250 milligrams of S-(-)-alpha-lipoic acid
10 milligrams of lactose
125 milligrams of hydroxypropyl emthylcelluloses
20 milligrams of ethyl celluloses
40 milligrams of 1.5% Gonaks
5 milligrams of Pulvis Talci
2 milligrams of magnesium stearate
Normal release raw material component and content are:
50 milligrams of S-(-)-alpha-lipoic acid
10 milligrams of starch
10 milligrams of 6% polyvinylpyrrolidonesolution solution
2 milligrams of Pulvis Talci
2 milligrams of magnesium stearate
The film-coat component and the content of this double-layer sustained release tablets are:
4 milligrams of hydroxypropyl emthylcelluloses
6 milligrams of PEG400s
0.5 milligram of titanium dioxide
1 milligram of Pulvis Talci
80 milliliters of food stage ethanol
20 milliliters in water
The preparation technology of double-layer tablet of the present invention is as follows:
Respectively S-(-)-alpha-lipoic acid, starch, hydroxypropyl emthylcellulose, ethyl cellulose, microcrystalline Cellulose, carboxymethyl starch sodium are pressed component of the present invention and content drying, pulverizing, crossed 100 mesh sieves respectively, standby.
The preparation technology of normal release raw material:
Respectively S-(-)-alpha-lipoic acid, starch, lactose, microcrystalline Cellulose being crossed 100 mesh sieves by content of the present invention mixes.Add 6% polyvinylpyrrolidonesolution solution and make soft material in right amount, with agglomerating, the light pressure of the holding degree of being that promptly looses; Crossing 18 eye mesh screens granulates; With 16 eye mesh screen granulate, add carboxymethyl starch sodium and lubricant, mix homogeneously is immediate-release granules.
The preparation technology of slow releasing pharmaceutical raw material:
Press component of the present invention and content with S-(-)-alpha-lipoic acid, starch, mistake 80 mesh sieve mix homogeneously.Lactose,, ethyl cellulose, microcrystalline Cellulose, hydroxypropyl emthylcellulose cross mix homogeneously behind 80 mesh sieves by content of the present invention.Again two kinds of mixture are crossed mix homogeneously behind 80 mesh sieves.Add 1.5% Gonak and make soft material in right amount, with the promptly diffusing degree of holding of being of agglomerating, light pressure; Crossing 18 eye mesh screens granulates; Drying is 2 hours under 45 ℃ of conditions; With 16 eye mesh screen granulate, add lubricant, mix homogeneously is slow-releasing granules.
Immediate-release granules and slow-releasing granules are placed the administration funnel respectively, use the bi-layer tablet press tabletting.
Film coating procedure:
The preparation of coating solution: in the ethanol with hydroxypropyl emthylcellulose adding 95%, under constantly stirring, add entry by component of the present invention and content, it is fully dissolved, add other raw materials of recipe quantity again, stirred 30-50 minute, promptly get coating solution.
Art for coating: plain sheet is removed fine powder add in the coating pan, be preheated to 30 ℃, regulate compressed air, making its pressure is 0.4Mpa, regulating the coating pan rotating speed is 3-10 rev/min, spray speed to the sheet of regulating spray gun heavily increased to 1% o'clock, stopped coating, and coated tablet is taken out from coating pan, put into the drying cupboard of desiccant, after at least 5 hours, take out check, packing promptly gets this product.
Described various components contents is the content of making 1 double-layer tablet of the present invention.
Embodiment 3
Principal agent is that the prescription of slow releasing tablet of the mixture of R-(+)-alpha-lipoic acid and S-(-)-alpha-lipoic acid is:
300 milligrams in the mixture of R-(+)-alpha-lipoic acid and S-(-)-alpha-lipoic acid
10 milligrams of lactose
125 milligrams of hydroxypropyl emthylcelluloses
20 milligrams of ethyl celluloses
40 milligrams of 1.5% Gonaks
5 milligrams of Pulvis Talci
2 milligrams of magnesium stearate
The film-coat component and the content of this layer slow releasing tablet are:
4 milligrams of hydroxypropyl emthylcelluloses
6 milligrams of PEG400s
0.5 milligram of titanium dioxide
1 milligram of Pulvis Talci
80 milliliters of food stage ethanol
20 milliliters in water
The preparation technology of this slow releasing tablet is as follows:
The mixture of R-(+)-alpha-lipoic acid and S-(-)-alpha-lipoic acid, starch, hydroxypropyl emthylcellulose, ethyl cellulose, microcrystalline Cellulose, carboxymethyl starch sodium by component of the present invention and content drying, pulverizing, are crossed 100 mesh sieves respectively, standby.
The preparation technology of slow releasing pharmaceutical raw material:
Press component of the present invention and content mixture, starch, mistake 80 mesh sieve mix homogeneously with R-(+)-alpha-lipoic acid and S-(-)-alpha-lipoic acid.Lactose,, ethyl cellulose, microcrystalline Cellulose, hydroxypropyl emthylcellulose cross mix homogeneously behind 80 mesh sieves by content of the present invention.Again two kinds of mixture are crossed mix homogeneously behind 80 mesh sieves.Add 1.5% Gonak and make soft material in right amount, with the promptly diffusing degree of holding of being of agglomerating, light pressure; Crossing 18 eye mesh screens granulates; Drying is 2 hours under 45 ℃ of conditions; With 16 eye mesh screen granulate, add lubricant, mix homogeneously is slow-releasing granules.
Slow-releasing granules is placed the administration funnel respectively, use the bi-layer tablet press tabletting.
Film coating procedure:
The preparation of coating solution: in the ethanol with hydroxypropyl emthylcellulose adding 95%, under constantly stirring, add entry by component of the present invention and content, it is fully dissolved, add other raw materials of recipe quantity again, stirred 30-50 minute, promptly get coating solution.
Art for coating: plain sheet is removed fine powder add in the coating pan, be preheated to 30 ℃, regulate compressed air, making its pressure is 0.4Mpa, regulating the coating pan rotating speed is 3-10 rev/min, spray speed to the sheet of regulating spray gun heavily increased to 1% o'clock, stopped coating, and coated tablet is taken out from coating pan, put into the drying cupboard of desiccant, after at least 5 hours, take out check, packing promptly gets this product.
Described various components contents is the content of making 1 double-layer tablet of the present invention.
Embodiment 4
Principal agent is that the prescription of the double-layer sustained release tablets of (+)-dihydrolipoic acid is:
(+)-dihydrolipoic acid slow releasing pharmaceutical raw material components and content are:
225 milligrams of (+)-dihydrolipoic acids
10 milligrams of lactose
100 milligrams of hydroxypropyl emthylcelluloses
20 milligrams of ethyl celluloses
40 milligrams of 1.5% Gonaks
5 milligrams of Pulvis Talci
2 milligrams of magnesium stearate
(+)-dihydrolipoic acid normal release raw material component and content are:
75 milligrams of (+)-dihydrolipoic acids
10 milligrams of starch
10 milligrams of 6% polyvinylpyrrolidonesolution solution
2 milligrams of Pulvis Talci
2 milligrams of magnesium stearate
The film-coat component and the content of this double-layer sustained release tablets are:
4 milligrams of hydroxypropyl emthylcelluloses
6 milligrams of PEG400s
0.5 milligram of titanium dioxide
1 milligram of Pulvis Talci
80 milliliters of food stage ethanol
20 milliliters in water
The preparation technology of this double-layer tablet is as follows:
Respectively (+)-dihydrolipoic acid, starch, hydroxypropyl emthylcellulose, ethyl cellulose, microcrystalline Cellulose, carboxymethyl starch sodium are pressed component of the present invention and content drying, pulverizing, crossed 100 mesh sieves respectively, standby.
The preparation technology of normal release raw material:
Respectively (+)-dihydrolipoic acid, starch, lactose, microcrystalline Cellulose being crossed 100 mesh sieves by content of the present invention mixes.Add 6% polyvinylpyrrolidonesolution solution and make soft material in right amount, with agglomerating, the light pressure of the holding degree of being that promptly looses; Crossing 18 eye mesh screens granulates; With 16 eye mesh screen granulate, add carboxymethyl starch sodium and lubricant, mix homogeneously is immediate-release granules.
The preparation technology of slow releasing pharmaceutical raw material:
Press component of the present invention and content with (+)-dihydrolipoic acid, starch, mistake 80 mesh sieve mix homogeneously.Lactose,, ethyl cellulose, microcrystalline Cellulose, hydroxypropyl emthylcellulose cross mix homogeneously behind 80 mesh sieves by content of the present invention.Again two kinds of mixture are crossed mix homogeneously behind 80 mesh sieves.Add 1.5% Gonak and make soft material in right amount, with the promptly diffusing degree of holding of being of agglomerating, light pressure; Crossing 18 eye mesh screens granulates; Drying is 2 hours under 45 ℃ of conditions; With 16 eye mesh screen granulate, add lubricant, mix homogeneously is slow-releasing granules.
Immediate-release granules and slow-releasing granules are placed the administration funnel respectively, use the bi-layer tablet press tabletting.
Film coating procedure:
The preparation of coating solution: in the ethanol with hydroxypropyl emthylcellulose adding 95%, under constantly stirring, add entry by component of the present invention and content, it is fully dissolved, add other raw materials of recipe quantity again, stirred 30-50 minute, promptly get coating solution.
Art for coating: plain sheet is removed fine powder add in the coating pan, be preheated to 30 ℃, regulate compressed air, making its pressure is 0.4Mpa, regulating the coating pan rotating speed is 3-10 rev/min, spray speed to the sheet of regulating spray gun heavily increased to 1% o'clock, stopped coating, and coated tablet is taken out from coating pan, put into the drying cupboard of desiccant, after at least 5 hours, take out check, packing promptly gets this product.
Described various components contents is the content of making 1 double-layer tablet of the present invention.
Embodiment 5
The prescription of principal agent (-)-dihydrolipoic acid double-layer sustained release tablets is:
(-)-dihydrolipoic acid slow releasing pharmaceutical raw material components and content are:
175 milligrams of (-)-dihydrolipoic acids
10 milligrams of lactose
100 milligrams of hydroxypropyl emthylcelluloses
20 milligrams of ethyl celluloses
40 milligrams of 1.5% Gonaks
5 milligrams of Pulvis Talci
2 milligrams of magnesium stearate
(-)-dihydrolipoic acid normal release raw material component and content are:
125 milligrams of (-)-dihydrolipoic acids
10 milligrams of starch
10 milligrams of 6% polyvinylpyrrolidonesolution solution
2 milligrams of Pulvis Talci
2 milligrams of magnesium stearate
The film-coat component and the content of this double-layer sustained release tablets are:
4 milligrams of hydroxypropyl emthylcelluloses
6 milligrams of PEG400s
0.5 milligram of titanium dioxide
1 milligram of Pulvis Talci
80 milliliters of food stage ethanol
20 milliliters in water
The preparation technology of this double-layer tablet is as follows:
Respectively (-)-dihydrolipoic acid, starch, hydroxypropyl emthylcellulose, ethyl cellulose, microcrystalline Cellulose, carboxymethyl starch sodium are pressed component of the present invention and content drying, pulverizing, crossed 100 mesh sieves respectively, standby.
The preparation technology of normal release raw material:
Respectively (-)-dihydrolipoic acid, starch, lactose, microcrystalline Cellulose being crossed 100 mesh sieves by content of the present invention mixes.Add 6% polyvinylpyrrolidonesolution solution and make soft material in right amount, with agglomerating, the light pressure of the holding degree of being that promptly looses; Crossing 18 eye mesh screens granulates; With 16 eye mesh screen granulate, add carboxymethyl starch sodium and lubricant, mix homogeneously is immediate-release granules.
The preparation technology of slow releasing pharmaceutical raw material:
Press component of the present invention and content with (-)-dihydrolipoic acid, starch, mistake 80 mesh sieve mix homogeneously.Lactose, ethyl cellulose, microcrystalline Cellulose, hydroxypropyl emthylcellulose are crossed mix homogeneously behind 80 mesh sieves by content of the present invention.Again two kinds of mixture are crossed mix homogeneously behind 80 mesh sieves.Add 1.5% Gonak and make soft material in right amount, with the promptly diffusing degree of holding of being of agglomerating, light pressure; Crossing 18 eye mesh screens granulates; Drying is 2 hours under 45 ℃ of conditions; With 16 eye mesh screen granulate, add lubricant, mix homogeneously is slow-releasing granules.
Immediate-release granules and slow-releasing granules are placed the administration funnel respectively, use the bi-layer tablet press tabletting.
Film coating procedure:
The preparation of coating solution: in the ethanol with hydroxypropyl emthylcellulose adding 95%, under constantly stirring, add entry by component of the present invention and content, it is fully dissolved, add other raw materials of recipe quantity again, stirred 30-50 minute, promptly get coating solution.
Art for coating: plain sheet is removed fine powder add in the coating pan, be preheated to 30 ℃, regulate compressed air, making its pressure is 0.4Mpa, regulating the coating pan rotating speed is 3-10 rev/min, spray speed to the sheet of regulating spray gun heavily increased to 1% o'clock, stopped coating, and coated tablet is taken out from coating pan, put into the drying cupboard of desiccant, after at least 5 hours, take out check, packing promptly gets this product.
Claims (7)
1. the slow releasing preparation of an alpha-lipoic acid or derivatives thereof is characterized in that with the alpha-lipoic acid or derivatives thereof as blocker, making slow releasing tablet with hydroxypropyl emthylcellulose as principal agent, and its component proportioning is as follows:
Principal agent 10-1000 milligram
Starch 0-60 milligram
Lactose 0-50 milligram
Hydroxypropyl emthylcellulose 10-1000 milligram
Ethyl cellulose 0-20 milligram
Microcrystalline Cellulose 0-200 milligram
1.5% Gonak 1-40 milligram
Pulvis Talci 1-5 milligram
Magnesium stearate 1-2 milligram.
2. the slow releasing preparation of alpha-lipoic acid or derivatives thereof according to claim 1, it is characterized in that with described slow releasing tablet component as slow release layer, increase on its basis one deck with the alpha-lipoic acid or derivatives thereof be principal agent often release layer, make double-layer tablet, the described component proportioning of often releasing layer is:
Principal agent 10-1000 milligram
Starch 1-60 milligram
Lactose 1-50 milligram
Ethyl cellulose 1-20 milligram
Microcrystalline Cellulose 1-200 milligram
6% polyvinylpyrrolidonesolution solution 1-40 milligram
Pulvis Talci 1-5 milligram
Magnesium stearate 1-2 milligram.
3. the slow releasing preparation of alpha-lipoic acid or derivatives thereof according to claim 1 and 2 is characterized in that the content of alpha-lipoic acid or derivatives thereof principal agent in slow release layer is the 20-800 milligram.
4. the slow releasing preparation of alpha-lipoic acid or derivatives thereof according to claim 2, it is characterized in that alpha-lipoic acid or derivatives thereof principal agent at slow release layer and the total content of often releasing in the layer be the 100-1000 milligram.
5. the slow releasing preparation of alpha-lipoic acid or derivatives thereof according to claim 4, it is characterized in that alpha-lipoic acid or derivatives thereof principal agent at slow release layer and the total content of often releasing in the layer be the 100-600 milligram.
6. the slow releasing preparation of alpha-lipoic acid or derivatives thereof according to claim 1 and 2 is characterized in that the R-(+) that described alpha-lipoic acid or derivatives thereof is racemic alpha-lipoic acid, enantiomer-pure-or (+)-dihydrolipoic acid or (-)-dihydrolipoic acid or its mixture of S-(-)-alpha-lipoic acid or its mixture, racemic dihydrolipoic acid, enantiomer-pure.
7. the preparation method of the slow releasing preparation of alpha-lipoic acid or derivatives thereof according to claim 2, each component that it is characterized in that respectively slow release layer and often release layer is fully mixed, and carry out wet granulation, make slow-releasing granules respectively and often release granule, again 5-70 ℃ of drying, behind dried granule granulate, place the administration funnel respectively often releasing granule and slow-releasing granules, be pressed into bilayer tablet with bi-layer tablet press.
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| CN 200610035954 CN1868463A (en) | 2006-06-15 | 2006-06-15 | Slow-release prepn. contg. alpha-lipoic acid or its derivatives, and preparing method therefor |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101543481B (en) * | 2008-03-28 | 2011-03-23 | 北京四环科宝制药有限公司 | Double-layer breviscapine sustained-release tablet and preparation method thereof |
| CN102469807A (en) * | 2009-07-14 | 2012-05-23 | 希尔氏宠物营养品公司 | Pet food compositions including a sustained-release lipoic acid and methods of manufacture and use thereof |
| CN104146981A (en) * | 2013-05-15 | 2014-11-19 | 北京韩美药品有限公司 | Lipoic acid composition and preparation method thereof |
| CN104688705A (en) * | 2015-02-09 | 2015-06-10 | 武汉泽智生物医药有限公司 | Alpha-lipoic acid sustained-release tablet and preparation method thereof |
| EP3366291A1 (en) | 2017-02-22 | 2018-08-29 | Montero Gida Sanayi Ve Ticaret A.S. | Solid oral pharmaceutical compositions comprising alpha lipoic acid and water-soluble vitamins |
| WO2022060333A1 (en) * | 2020-09-21 | 2022-03-24 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | A pharmaceutical bilayer tablet comprising alpha lipoic acid and at least one b vitamin |
-
2006
- 2006-06-15 CN CN 200610035954 patent/CN1868463A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101543481B (en) * | 2008-03-28 | 2011-03-23 | 北京四环科宝制药有限公司 | Double-layer breviscapine sustained-release tablet and preparation method thereof |
| CN102469807A (en) * | 2009-07-14 | 2012-05-23 | 希尔氏宠物营养品公司 | Pet food compositions including a sustained-release lipoic acid and methods of manufacture and use thereof |
| CN105639121A (en) * | 2009-07-14 | 2016-06-08 | 希尔氏宠物营养品公司 | Pet food compositions including a sustained-release lipoic acid and methods of manufacture and use thereof |
| CN104146981A (en) * | 2013-05-15 | 2014-11-19 | 北京韩美药品有限公司 | Lipoic acid composition and preparation method thereof |
| CN104146981B (en) * | 2013-05-15 | 2018-06-19 | 北京韩美药品有限公司 | A kind of lipoic acid composition and preparation method thereof |
| CN104688705A (en) * | 2015-02-09 | 2015-06-10 | 武汉泽智生物医药有限公司 | Alpha-lipoic acid sustained-release tablet and preparation method thereof |
| CN104688705B (en) * | 2015-02-09 | 2017-07-25 | 武汉泽智生物医药有限公司 | A kind of alpha lipoic acid sustained release tablets and preparation method thereof |
| EP3366291A1 (en) | 2017-02-22 | 2018-08-29 | Montero Gida Sanayi Ve Ticaret A.S. | Solid oral pharmaceutical compositions comprising alpha lipoic acid and water-soluble vitamins |
| WO2018153914A1 (en) | 2017-02-22 | 2018-08-30 | Montero Gida Sanayi Ve Ticaret A.S. | Solid oral pharmaceutical compositions comprising alpha lipoic acid and water-soluble vitamins |
| WO2022060333A1 (en) * | 2020-09-21 | 2022-03-24 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | A pharmaceutical bilayer tablet comprising alpha lipoic acid and at least one b vitamin |
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