CN1650976A - Compound saussurea involucrata capsule and its preparation process - Google Patents
Compound saussurea involucrata capsule and its preparation process Download PDFInfo
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Abstract
A compound snow lotus softgel is composed of the core prepared from extract and volatile oil of raw Chinese-medicinal materials, antioxidizing agent, sterilizer and diluent, and the shell prepared from gelatin, plasticizer, antiseptic, masking agent, pigment, flavouring and water. It can be used for treating rheumatic arthritis, rheumatoid arthritis, tonic rachitis, retrograde osteoarthropathy, etc.
Description
The present invention relates to-kind adopt compound saussurea involucrata capsule of making after Chinese herbal medicine extractum or Chinese herbal medicine extract powder and the mixed with excipients and preparation method thereof.
[background technology]
FUFANG XUELIAN JIAONANG is the ethnic drug in Xinjiang, is recorded by Drug Standard of Ministry of Public Health of the Peoples Republic of China (" Chinese traditional patent formulation preparation " the 19).
[prescription] Herba Saussureae Involueratae: 720 gram Rhizoma Corydalis (vinegar system): 180 gram Rhizoma Et Radix Notopterygiis: 180 grams
Radix Aconiti (system): 60 gram Radix Angelicae Pubescentiss: 180 gram Radix Aconiti Kusnezoffii (system), 60 grams
Fructus Chaenomelis 180 gram Cortex Periplocaes 240 grams
[method for making] above eight flavors, Herba Saussureae Involueratae are with 65% alcohol reflux three times, merge extractive liquid,, and filtration, decompression filtrate recycling ethanol is concentrated into thick paste, and drying under reduced pressure becomes dried cream.Seven flavors such as all the other Rhizoma Corydalis decoct with water secondary, and each 2 hours, collecting decoction filtered, and filtrate decompression is concentrated into 1: 1, and concentrated solution was measured 40% ethanol precipitations 24 hours with 3 times, got supernatant and reclaimed ethanol, concentrated, and drying under reduced pressure becomes dried cream.Above-mentioned two kinds of dried cream are mixed, pulverize, sieve, incapsulate, make.
[function with cure mainly] dispelling cold by warming the meridian dispels the wind by wet blood stasis dispersing and deswelling, relaxing muscles and tendons and activating QI and blood in the collateral.Be used for wind-cold damp pathogen, numbness hinders meridians institute to rheumatoid arthritis, rheumatic arthritis, ankylosing spondylitis and all kinds of degenerative osteoarthritis.
Monarch drug Herba Saussureae Involueratae in the FUFANG XUELIAN JIAONANG is the ethnic drug in Xinjiang, and the herb or the aerial parts of Compositae (compositae) hieracioides platymiscium are grown in the snow line crack of stone about height above sea level three kms." Xinjiang Chinese herbal medicine " record: " Herba Saussureae Involueratae; warm in nature, little hardship; function expelling wind and removing dampness ", has special-effect to curing rheumatism, its contained polyhydroxy Herba Saussureae Involueratae flavone has effects such as antiinflammatory, rheumatism, analgesia, be the ethnic drug commonly used medicine among the people of plateau refrigerant latitudes such as Tibet, Xinjiang, Qinghai, Gansu, Yunnan, Sichuan, the legend of " the wonderful effect of outstanding service " is arranged between the ethnic groups of Xinjiang.
Rheumatism is a frequently-occurring disease now, at present, no matter be at home or external, it is not within minority to suffer from rheumatismal people, and this disease is the chronic disease of comparison refractory, easily recurrence, the development of appointing then can cause joint maimed person in various degree, influence working and learning, severe patient be can't take care of oneself, and is called " a kind of cancer that can be not dead " by people.The mechanism that all establishment is relevant of most of in the world country carries out research in this respect specially, is devoted to remove rheumatisant's misery.
FUFANG XUELIAN JIAONANG exists problem in production, process of clinical application, specific as follows:
1, Chinese medicine extract such as Herba Saussureae Involueratae, Rhizoma Corydalis draw moist very strong, in existing specification, can't make granule, can only Chinese medicine extract can occur as the hard capsule of packing into powder type is bonded to bar-shaped, in humidity upper zone such as south, the softgel shell dissolution phenomena can occur, compound saussurea involucrata capsule has solved this problem, makes product more stable.
2, effect experiment:, can to rat assist agent arthritis, two kinds of inflammatory models of rat carrageenan the obvious suppression effect be arranged all by the description compound saussurea involucrata capsule by the experimental data in the description; Simultaneously, can reduce the acetic acid induced mice and turn round the body number of times.Show: compound saussurea involucrata capsule has tangible antiinflammatory, analgesic activity, thereby provides the pharmacology foundation for its clinical treatment rheumatic arthritis, rheumatoid arthritis.And the compound saussurea involucrata capsule effect obviously is better than FUFANG XUELIAN JIAONANG.
3, stripping experiment: by the experimental data in the description, the dissolution that compound saussurea involucrata capsule can be described is faster than hard capsule, dependency according to bioavailability in dissolution in vitro and the body can be inferred, after FUFANG XUELIAN JIAONANG is made soft capsule, not only overcome shortcomings such as the easy moisture absorption of hard capsule dosage form, poor stability, and can improve the bioavailability of preparation.
[summary of the invention]
The invention provides a kind of rheumatoid arthritis that is used for, rheumatic arthritis, the compound saussurea involucrata capsule of ankylosing spondylitis and all kinds of degenerative osteoarthritis diseases associated and symptom, its steady quality, safety, easy to use.The present invention also provides a kind of compound saussurea involucrata capsule preparation technology.
Its capsule core material of a kind of compound saussurea involucrata capsule contains following composition by weight percentage: volatile oil, pharmaceutic adjuvant that 10～70% Chinese medicine extract or above-mentioned Chinese medicine extract corresponding amount Chinese medicine extraction obtain.The antioxidant of pharmaceutic adjuvant bag Chinese juniper 0～2%, 0～20% capsulation stabilizer and proper amount of diluting.Its softgel shell contains 35～45% gelatin, 18～22% plasticizer, 0.08～0.11% antiseptic, 0～3% screening agent, 0～10% Polyethylene Glycol, 0～1% pigment, 0～0.1% correctives and an amount of water by raw material weight percentage ratio.
Above-mentioned diluent comprises one or more in Oleum Arachidis hypogaeae semen, Oleum Glycines, safflower oil, Oleum Hippophae, Oleum Camelliae, salad oil, Polyethylene Glycol, the corn wet goods.
Above-mentioned capsulation stabilizer comprises one or more in Cera Flava, Adeps caprae seu ovis, methylcellulose, ethyl cellulose, Polyethylene Glycol monostearate, tween 80, Polyethylene Glycol, poloxamer, the glycerol.
Above-mentioned antioxidant comprises one or more in vitamin E, tea polyphenols, tertiarybutylhydroquinone, Radix Glycyrrhizae antioxygen thing, Butylated hydroxyanisole, dibenzylatiooluene, the propyl gallate.
Above-mentioned plasticizer comprises one or more in glycerol, sorbitol, the sucrose.
Foregoing preservatives comprises one or more in methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, the butyl p-hydroxybenzoate.
Above-mentioned screening agent comprises one or more in titanium dioxide, barium sulfate, ferrum oxide, the calcium carbonate.
Above-mentioned pigment comprises lemon yellow, amaranth, carmine, cacao brown, white carbon black, in light green, greyish purple one or more.
Above-mentioned correctives comprises one or more in bourbonal,ethyl vanillin, essential oil, the Mentholum.
Compound saussurea involucrata capsule is to be undertaken by following step:
The capsule core material preparation: amount takes by weighing the Herba Saussureae Involueratae that is up to the standards at first in accordance with regulations, 8～12 times of 55～70% soak with ethanol of adding Herba Saussureae Involueratae weight 12 hours, reflux, extract, three times each 1.5 hours, merges three times extracting solution, filter, decompression filtrate recycling ethanol is condensed into thick paste, or is dried to dried cream, be ground into the above fine powder of 80 orders, standby.8～12 times of water gagings that 7 flavor Chinese medicines such as all the other Rhizoma Corydalis add medical material weight soaked 12 hours, decoct twice each two hours, merge decocting liquid twice, filter, filtrate decompression is concentrated into 1: 1 (weight of concentrated solution and the ratio that drops into Chinese medicine weight), concentrated solution is precipitating 24～48 hours under 5～25 ℃ of temperature or adding to 95% edible ethanol that to contain alcoholic degree be 20～50% to precipitate and spend the night under 5～25 ℃ of temperature with 3 times of amount 40% ethanol, get the supernatant decompression recycling ethanol, be condensed into thick paste, or be dried to dried cream, be ground into the above fine powder of 80 orders, standby.Or 7 flavor Chinese medicines such as all the other Rhizoma Corydalis add 8～12 times of water gagings and soaked 0～12 hour, vapor distillation extracts volatile oil, distillation time 2～12 hours, extract 1～3 time, collect volatile oil, aqueous solution after distillation device is in addition collected, medicinal residues add 8～12 times of water gagings again and decocted 0.5～2 hour, filter, aqueous solution after filtrate and the distillation merges, and filters, and filtrate decompression is concentrated into 1: 1, concentrated solution is precipitating 24～48 hours under 5～25 ℃ of temperature or adding to 95% edible ethanol that to contain alcoholic degree be 20～50% to precipitate and spend the night under 5～25 ℃ of temperature with 3 times of amount 40% ethanol, get the supernatant decompression recycling ethanol, be condensed into thick paste, or be dried to dried cream, be ground into the above fine powder of 80 orders, standby.Secondly with above-mentioned two groups of equivalent extract mix homogeneously or with above-mentioned two groups of extract powder mix homogeneously, add capsulation stabilizer, diluent, antioxidant, mix homogeneously is crossed colloid mill, and is standby; Or, adding volatile oil, capsulation stabilizer, diluent, antioxidant with two groups of equivalent extract mix homogeneously or with above-mentioned two groups of extract powder mix homogeneously, mix homogeneously is crossed colloid mill, and is standby.
Softgel shell preparation: water, plasticizer, the antiseptic of aequum added to have in the interlayer stainless-steel pan that stirs decompressor stir, as first liquid; The gelatin of aequum is joined in the rustless steel jacketed pan that fills first liquid, and temperature is controlled at the room temperature stirring of constantly reducing pressure, and treats that gelatin grain expansion post-heating to 50～80 ℃ makes the gelatin grain all melt and dissolved; The screening agent, the pigment that add aequum under stirring continue decompression and stirred 30～120 minutes; Even melt and dissolved liquid filters, the filtrate insulation is left standstill or the degassing of reducing pressure stand-by.
The soft capsule compacting: it is poor that capsule core material is put into liquid storage, uses rotating mould platen press compacting soft capsule: wash ball, drying then, be packaged to be compound saussurea involucrata capsule.
Compound saussurea involucrata capsule of the present invention, constant product quality, its bioavailability of other dosage form is higher relatively, absorption is better, under the clinical dosage condition, be safe, to rheumatoid arthritis, rheumatic arthritis, ankylosing spondylitis and all kinds of degenerative osteoarthritis have definite therapeutical effect.
[specific embodiment]
The present invention is not subjected to the restriction of following embodiment, can determine concrete embodiment according to the technical scheme and the practical situation of the invention described above.
Embodiment 1, and the softgel shell of this compound saussurea involucrata capsule contains by weight percentage: 35% gelatin, 18% glycerol, 0.08% the methyl parahydroxybenzoate and the water of surplus; The capsule core material of this compound saussurea involucrata capsule contains by weight percentage: 10% Chinese medicine extract, 5% Cera Flava, 2% vitamin E and the safflower oil of surplus.
Embodiment 2, and the softgel shell of this compound saussurea involucrata capsule contains by weight percentage: 36% gelatin, 10% glycerol, 10% sorbitol, 0.10% the ethylparaben and the water of surplus; The capsule core material of this compound saussurea involucrata capsule contains by weight percentage: 15% Chinese medicine extract, and 5% Adeps caprae seu ovis, 3% Polyethylene Glycol, 3% glycerol, 1.5% tea polyphenols, 33% Oleum Hippophae and surplus Oleum Glycines.
Embodiment 3, and the softgel shell of this compound saussurea involucrata capsule contains by weight percentage: 37% gelatin, 22% sorbitol, 0.11 methyl parahydroxybenzoate, 0.35% lemon yellow, 0.07% ethyl vanillin, 1% the titanium dioxide and the water of surplus; The capsule core material of this compound saussurea involucrata capsule contains by weight percentage: 20% Chinese medicine extract, 15% methylcellulose, 5% Polyethylene Glycol monostearate, 1% Butylated hydroxyanisole, 6% Oleum Camelliae and the salad oil of surplus.
Embodiment 4, and the softgel shell of this compound saussurea involucrata capsule contains by weight percentage: 38% gelatin, 12% sorbitol, 10% sucrose, 0.08% methyl parahydroxybenzoate, 0.02% propyl p-hydroxybenzoate, 0.1% amaranth, 0.5% the barium sulfate and the water of surplus; The capsule core material of this compound saussurea involucrata capsule contains by weight percentage: 25% Chinese medicine extract, 10% ethyl cellulose, 2% tween 80,4% poloxamer, 1.5% tertiarybutylhydroquinone and the Semen Maydis oil of surplus.
Embodiment 6, and the softgel shell of this compound saussurea involucrata capsule contains by weight percentage: 40% gelatin, 21% glycerol, 0.09% ethylparaben, 0.28% cacao brown, 0.06% titanium dioxide, 0.68% the ferrum oxide and the water of surplus; The capsule core material of this compound saussurea involucrata capsule contains by weight percentage: 35% Chinese medicine extract, 6% Polyethylene Glycol, 4% poloxamer, 1.5% propyl gallate, 8% Oleum Hippophae, 15.5% Semen Maydis oil and the Oleum Arachidis hypogaeae semen of surplus.
Embodiment 7, and the softgel shell of this compound saussurea involucrata capsule contains by weight percentage: 41% gelatin, 15% glycerol, 3% sucrose, 0.1% butyl p-hydroxybenzoate, 0.12 cacao brown, 0.01% the essential oil and the water of surplus; The capsule core material of this compound saussurea involucrata capsule contains by weight percentage: 40% Chinese medicine extract, 8% Polyethylene Glycol, 5% poloxamer, 2% Radix Glycyrrhizae polyphenoils, 30% safflower oil, the volatile oil that above-mentioned Chinese medicine extract corresponding amount Chinese medicine extraction obtains and the salad oil of surplus.
Embodiment 8, the softgel shell of this compound saussurea involucrata capsule contains by weight percentage: 42% gelatin, 21% glycerol, 0.08% methyl parahydroxybenzoate, 0.02% propyl p-hydroxybenzoate, 0.28% light green, 0.8% the titanium dioxide and the water of surplus: the capsule core material of this compound saussurea involucrata capsule contains by weight percentage: 45% Chinese medicine extract, 3% ethyl cellulose, 5% Polyethylene Glycol, 2% glycerol, 1% vitamin E, 0.5% propyl gallate, 13.5% Oleum Glycines, the volatile oil that above-mentioned Chinese medicine extraction corresponding amount Chinese medicine extraction obtains and the safflower oil of surplus.
Embodiment 9, and the softgel shell of this compound saussurea involucrata capsule contains by weight percentage: 43% gelatin, 20% glycerol, 0.1% ethylparaben, 0.2% light green, 0.75% the barium sulfate and the water of surplus; The capsule core material of this compound saussurea involucrata capsule contains by weight percentage: 50% Chinese medicine extract, 5% ethyl cellulose, 8% Polyethylene Glycol, 1% Butylated hydroxyanisole, 1% propyl gallate and the Oleum Glycines of surplus.
Embodiment 10, and the softgel shell of this compound saussurea involucrata capsule contains by weight percentage: 44% gelatin, 22% glycerol, 0.08% butyl p-hydroxybenzoate, 0.18% white carbon black, 0.65% the titanium dioxide and the water of surplus; The capsule core material of this compound saussurea involucrata capsule contains by weight percentage: 55% Chinese medicine extract, 5% Polyethylene Glycol, 4% poloxamer, 1% Radix Glycyrrhizae polyphenoils, 1% dibenzylatiooluene and the Oleum Glycines of surplus.
Embodiment 11, and the softgel shell of this compound saussurea involucrata capsule contains by weight percentage: 45% gelatin, 18% glycerol, 0.1% the carmine and the water of surplus; The capsule core material of this compound saussurea involucrata capsule contains by weight percentage: 60% Chinese medicine extract, 2.5% tween 80,5% glycerol and the Polyethylene Glycol of surplus.
Embodiment 12, the softgel shell of this compound saussurea involucrata capsule contains by weight percentage: 38.5 gelatin, 20% glycerol, 0.08% methyl parahydroxybenzoate, 0.02% propyl p-hydroxybenzoate, 0.28% amaranth, 0.03% bourbonal,ethyl vanillin, 0.07% Mentholum, 0.76% the titanium dioxide and the water of surplus; The capsule core material of this compound saussurea involucrata capsule contains by weight percentage: 65% Chinese medicine extract, 2.5% poloxamer, 2% Radix Glycyrrhizae polyphenoils, the volatile oil that above-mentioned Chinese medicine extract corresponding amount Chinese medicine extraction obtains and the Oleum Arachidis hypogaeae semen of surplus.
Embodiment 13, and the softgel shell of this compound saussurea involucrata capsule contains by weight percentage: 41% gelatin, 19% glycerol, 0.11% ethylparaben, 0.24% cacao brown, 0.04% essential oil, 0.04% essential oil, 0.88% the titanium dioxide and the water of surplus; The capsule core material of this compound saussurea involucrata capsule contains by weight percentage: 70% the Chinese medicine extract and the Polyethylene Glycol of surplus.
Compound saussurea involucrata capsule in the foregoing description can obtain by following production method: the capsule core material preparation: amount takes by weighing the Herba Saussureae Involueratae that is up to the standards at first in accordance with regulations, add the soak with ethanol 12 hours of 8 times or 9 times or 10 times or 11 times or 12 times, concentration of alcohol is 50% or 55% or 60% or 65% or 70%, reflux, extract, three times, each 1.5 hours, merge extractive liquid, filters decompression filtrate recycling ethanol, be condensed into thick paste, or be dried to dried cream, and be ground into the above fine powder of 80 orders, standby.All the other Rhizoma Corydalis etc. 7 flavor Chinese medicines add the water logging bubble 12 hours of 8 times or 9 times or 10 times or 11 times or 12 times, decoct twice, each 2 hours, collecting decoction, filter, filtrate decompression is concentrated into 1: 1, and concentrated solution is reduced to room temperature, add 3 times of amount 40% ethanol, precipitation is 12 hours or 24 hours or 36 hours or 48 hours under 5 ℃ or 10 ℃ or 15 ℃ or 20 ℃ or 25 ℃ of temperature, gets the supernatant decompression recycling ethanol, is condensed into thick paste, or be dried to dried cream, be ground into the above fine powder of 80 orders.Or the concentrated solution that was evaporated to 1: 1 adds to 95% edible ethanol, and to contain alcoholic degree be 20% or 25% or 30% or 35% or 40% or 45% or 50%, under 5 ℃ or 10 ℃ or 15 ℃ or 20 ℃ or 25 ℃ of temperature, precipitate and spend the night, get the supernatant decompression recycling ethanol, be condensed into thick paste, or be dried to dried cream, be ground into the above fine powder of 80 orders.Or 7 flavor Chinese medicines such as all the other Rhizoma Corydalis add 8 times or 9 times or 10 times or 11 times or 12 times of water gagings soaked 0 hour or 2 hours or 4 hours or 6 hours or 8 hours or 10 hours or 12 hours, vapor distillation extracts volatile oil, distillation time 2 hours or 4 hours or 6 hours or 8 hours or 10 hours or 12 hours, extract 1 time or 2 times or 3 times, collect volatile oil, aqueous solution after distillation device is in addition collected, medicinal residues add 8 times or 9 times or 10 times or 11 times again or 12 times of water gagings decocted 0.5 hour or 1 hour or 1.5 hours or 2 hours, filter, aqueous solution after filtrate and the distillation merges, filter, filtrate decompression is concentrated into 1: 1, concentrated solution with 3 times of amount 40% ethanol precipitation under 5 ℃ or 10 ℃ or 15 ℃ or 20 ℃ or 25 ℃ of temperature 12 hours or 24 hours or 36 hours or 48 hours, get the supernatant decompression recycling ethanol, be condensed into thick paste, or be dried to dried cream, be ground into the above fine powder of 80 orders, standby.Or the concentrated solution that was evaporated to 1: 1 adds to 95% edible ethanol, and to contain alcoholic degree be 20% or 25% or 30% or 35% or 40% or 45% or 50%, under 5 ℃ or 10 ℃ or 15 ℃ or 20 ℃ or 25 ℃ of temperature, precipitate and spend the night, get the supernatant decompression recycling ethanol, be condensed into thick paste, or be dried to dried cream, be ground into the above fine powder of 80 orders, standby.Secondly with above-mentioned two groups of equivalent extract mix homogeneously or with above-mentioned two groups of extract powder mix homogeneously, add capsulation stabilizer, diluent, antioxidant, mix homogeneously is crossed colloid mill, and is standby; Or, adding volatile oil, capsulation stabilizer, diluent, antioxidant with above-mentioned two groups of equivalent extract mix homogeneously or with above-mentioned two groups of extract powder mix homogeneously, mix homogeneously is crossed colloid mill, and is standby.
The capsule leather is equipped with: water, plasticizer, the antiseptic of aequum added to have in the interlayer stainless-steel pan that stirs decompressor stir, as first liquid; The gelatin of aequum is joined in the rustless steel jacketed pan that fills first liquid, and temperature is controlled at the room temperature stirring of constantly reducing pressure, and treats that gelatin grain expansion post-heating to 50 ℃ or 60 ℃ or 70 ℃ or 80 ℃ make the gelatin grain all melt and dissolved; The screening agent, the pigment that add aequum under stirring continue decompression and stirred 30 minutes or 60 minutes or 90 minutes or 120 minutes; Even melt and dissolved liquid filters, the filtrate insulation is left standstill or the degassing of reducing pressure stand-by.
The soft capsule compacting: it is poor that capsule core material is put into liquid storage, uses rotating mould platen press compacting soft capsule; Wash ball, drying then, be packaged to be compound saussurea involucrata capsule.
Be that compound saussurea involucrata capsule and FUFANG XUELIAN JIAONANG compare to the foregoing description products obtained therefrom below, particular content is as follows:
One, compound saussurea involucrata capsule and FUFANG XUELIAN JIAONANG main pharmacodynamics are relatively
1 experiment material
1.1 be subjected to reagent thing compound saussurea involucrata capsule, lot number 20040316, Tefeng Pharmaceutical Co Ltd, Xinjiang's development, every 0.5g.FUFANG XUELIAN JIAONANG, the accurate word Z65020059 of traditional Chinese medicines, Xinjiang Chinese medicine head factory is produced, lot number 030708, every 0.3g, every corresponding medical material amount of compound saussurea involucrata capsule and FUFANG XUELIAN JIAONANG is consistent.
1.2 animal subject Wistar rat, body weight 130～180g.Kunming mouse, body weight 18-22g, male and female half and half.Xinjiang Medicine University's medical experiment animal center provides (No. the (2001)-16003, the moving word of new doctor).
1.3 equipment and reagent micrometer (Qinghai measuring instruments and cutting tools plant).Freund ' s Freund's complete adjuvant provides (lot number 2003009) by Bio Basic Inc.Carrageenin, U.S. Sigma company product.Glacial acetic acid, Xi'an chemical reagent factory product, lot number 020701.
1.4 test chamber condition Animal House entire area 120m
2, toy chamber area 20～25m
2, 23 ± 1 ℃ of room temperatures, humidity 40～60% has air cleaner.
2 methods and result
2.1 48 of Wistar male rats are got in the influence of adjuvant arthritis rats, and body weight 152.5 ± 15.2g is divided into 4 groups at random according to body weight, sex, that is: normal saline matched group, model group and hard capsule group and soft capsule group, 12 every group.The ig administration, once a day, successive administration 20 days.After the administration in first day 1 hour, every Mus was in left back sufficient subcutaneous injection Freund ' s Freund's complete adjuvant 0.1ml.Measure left and right sufficient sole of the foot thickness to 22 day with micrometer callipers every other day for every group, and observe the situation that Mus ear erythema, afterbody tuberosity etc. occur.Calculating is also compared each treated animal at different time pedal swelling degree and suppression ratio, relatively the drug effect of different dosage form.
The scorching front foot sole of the foot thickness of the scorching metapedes sole of the foot thickness of swelling degree=cause-cause
As a result, the left back sufficient sole of the foot injection adjuvant swelling next day degree of matched group obviously increases, and increases the weight of day by day.Secondary swelling occurs after the 15th day, and because of General Symptoms appears in delayed hypersensitive reaction, as the swelling of offside hind leg, the back is stiff etc.Its comparing result is: compare with model group, compound saussurea involucrata capsule and FUFANG XUELIAN JIAONANG all have significant difference; Compound saussurea involucrata capsule and FUFANG XUELIAN JIAONANG relatively also have significant difference; Therefore, compound saussurea involucrata capsule has the obvious suppression effect to rat by early stage inflammatory reaction and the swelling once again that adjuvant causes, effect is better than capsule.Each treated animal sees the following form 1 and table 2 at different time pedal swelling degree and suppression ratio.
Table 1: different Herba Saussureae Involueratae preparations are to the influence (primary injury) of rat assist agent arthritis left side paw swelling
The dosage number of animals cause scorching back different time (my god) swelling value x ± SD
Group g/kg (only)
2 4 6 8 10 12 14 16 18 20 22
0.22
0.00± 0.03± 0.03± 0.09± 0.15± 0.18± 0.17± 0.20± 0.22± 0.19±
NS - 12 ±
0.04 0.09 0.07 0.10 0.14 0.15 0.14 0.13 0.12 0.11 0.15
2.12
4.30± 4.41± 4.33± 3.89 3.42 3.12 2.87 2.56± 1.89± 1.74±
Model ±
- 12
Group 0.67* 0.75* 0.71* 0.39* 0.50* 0.46* 0.39* 0.47 0.45* 0.40*
0.50**
* * * * * * * ** * *
1.91
4.08± 3.82± 3.49 3.10 2.89 2.44 2.13 2.13± 1.88± 1.38±
±
Capsule
0.125?12 0.67 0.82 0.77+ 0.81+ 0.30+ 0.50+ 0.37+ 0.30+ 0.23 0.38 0.45
(9.9
(5.3) (13.3) (24.5) (20.3) (15.5) (21.8) (25.9) (16.8) (0.5) (20.7)
)
1.63
4.27± 4.04± 3.20± 2.63± 2.33± 1.98 1.82 1.64± 1.44± 1.23±
±
Flexible glue 0.47+ 0.44+ 0.41+ 0.54+ 0.48+ 0.28+ 0.27 0.32+ 0.36+
Capsule 0.208 12 0.46 0.38
+ + +▲▲ +▲ + +▲ + +▲ +
(23.
(0.7) (8.3) (26.0) (32.4 (31.9 (36.5) (36.6) (35.9) (23.8) (29.3)
1)
Compare * P＜0.05, * * P＜0.01 with the NS group; Compare with model group ,+P＜0.05, ++ in P＜0.01, () is suppression ratio %; Compare with the hard capsule group, ▲ P＜0.05, ▲ ▲ P＜0.01, be suppression ratio % in ()
Table 2: different Herba Saussureae Involueratae preparations are to the not influence of the right paw swelling of injection adjuvant (secondary injury) of rat
The dosage number of animals causes the swelling degree x ± SD of scorching back different time
Group
G/kg (only) 10 12 14 16 18 20 22
0.10± 0.18± 0.20± 0.30± 0.24± 0.25± 0.25±
NS - 12
0.08 0.12 0.10 0.10 0.14 0.15 0.13
0.28± 0.31 0.31 0.40± 0.36± 0.36± 0.35±
Model group-12
0.05* 0.15* 0.12* 0.11 0.11* 0.10 0.10*
0.25± 0.30 0.30± 0.29 0.32± 0.28± 0.31±
Capsule 0.125 12 0.08 0.08 0.09 0.08 0.12 0.11 0.17
(10.7) (3.2 (3.2 (27.5 (11.1) (23.2) (12.2)
0.20± 0.21 0.20 0.21 0.23 0.22 0.25±
0.05+ 0.09+ 0.10+ 0.09++ 0.10+
Soft capsule 0.208 12 0.07++ 0.12+
+ ▲ ▲ ▲ +
(28.6) (32.2 (35.5 (47.5 (36.1 (38.9 (28.1)
Compare * P＜0.05, * * P＜0.01 with the NS group; Compare with model group ,+P＜0.05, ++ P＜0.01; Compare with the hard capsule group, ▲ P＜0.05, ▲ ▲ P＜0.01, be suppression ratio % in ()
2.2 on Carrageenan causes the influence of rat paw edema
Get 40 of rats, body weight 144.4 ± 9.1g, male and female half and half are divided into 3 groups at random according to body weight, sex, that is: normal saline matched group and hard capsule group and soft capsule group, 10 every group.The ig administration, once a day, continuous five days.Behind the last administration 1.5h, under aseptic technique, 1% carrageenin, the 50 μ l that inject sterilization down for the right sufficient plantar aponeurosis of rat with No. 4 half syringe needles cause inflammation.Adopt to measure the right back sufficient sole of the foot thickness method of rat, measure cause scorching before and cause scorching back 1h, 2h, 3h, 5h, the right back sufficient sole of the foot thickness of 7h so that before and after scorching the difference of sufficient sole of the foot thickness as the swelling degree.Calculate and respectively organize rat toes swelling degree average and standard deviation, and calculate suppression ratio, do the t check.The results are shown in Table 3.
The scorching front foot sole of the foot thickness of the scorching metapedes sole of the foot thickness of swelling degree=cause-cause
Table 3: different Herba Saussureae Involueratae preparations cause the influence of rat paw edema to carrageenin
The dosage number of animals causes scorching back different time (h) swelling value x ± SD
Group
(g/kg) (only) 12357
NS to 0.58 ± 0.80 ± 1.05 ± 1.07 ± 0.95 ±
- 10
According to group 0.09 0.14 0.31 0.33 0.28
0.48± 0.65± 0.77± 0.75± 0.74±
Capsule 0.125 10 0.11* 0.15* 0.22* 0.35* 0.27
(17.2) (18.8) (26.7) (29.9) (22.1)
0.37± 0.50± 0.64± 0.60± 0.55±
0.09** 0.11**
Soft capsule 0.208 10 0.25** 0.24** 0.24**
+ +
(36.2) (37.5) (39.0) (43.9) (42.1)
Compare * * P＜0.05, * * P＜0.01 with matched group; Compare with the hard capsule group ,+P＜0.05, ++ in P＜0.01, () is suppression ratio %
Its comparing result is: compare with the NS matched group, compound saussurea involucrata capsule and FUFANG XUELIAN JIAONANG all have significant difference; Compound saussurea involucrata capsule and FUFANG XUELIAN JIAONANG relatively also have significant difference; Therefore, compound saussurea involucrata capsule can reduce carrageenin and cause the rat paw edema degree, and tangible antiinflammatory action is arranged, and effect is better than capsule.
2.3 Dichlorodiphenyl Acetate causes the influence of mouse writhing
Get 30 of Kunming mouses, body weight 20.1 ± 1.4g, the male and female dual-purpose, male and female half and half are divided into 3 groups at random according to body weight, sex, that is: normal saline matched group and hard capsule group and soft capsule group, 10 every group.The ig administration, every day 1 time, for three days on end.In last administration 1.5-2h, every Mus ip 0.6% acetic acid solution 0.2ml/ only.Observe after 5 minutes and record mice 15min in turn round body number of times (abdominal part indent, trunk are upheld with back leg, buttocks is raised, about health twist), have or not analgesic activity according to turning round body number of times judgement medicine.Experimental data is done statistical analysis, calculates the suppression ratio of medicine.The results are shown in Table 4.
The different Herba Saussureae Involueratae preparation of table 4 Dichlorodiphenyl Acetate causes the influence of mouse writhing reaction
Group dosage (g/kg) number of animals is turned round body number of times suppression ratio
(only) (x ± SD) (%)
NS group-10 31.7 ± 18.3-
Capsules group 0.18 10 18.4 ± 7.4* 41.96
Soft capsule group 0.30 10 10.9 ± 6.8**+ 65.61
Compare * P＜0.05, * * P＜0.01 with the NS group; Compare+P＜0.05 with the hard capsule group
Its comparing result is: compare with the NS matched group, compound saussurea involucrata capsule and FUFANG XUELIAN JIAONANG all have significant difference; Compound saussurea involucrata capsule and FUFANG XUELIAN JIAONANG relatively also have significant difference; Therefore, the compound saussurea involucrata capsule Dichlorodiphenyl Acetate causes the mouse writhing number average tangible reduction effect, and effect is better than capsule.
3 conclusions and discussion
Comprehensive above-mentioned three effect experiments, compound saussurea involucrata capsule all has the obvious suppression effect to rat assist agent arthritis, two kinds of inflammatory models of rat carrageenan; Simultaneously, can reduce the acetic acid induced mice and turn round the body number of times.Show: compound saussurea involucrata capsule has tangible antiinflammatory, analgesic activity, thereby provides the pharmacology foundation for its clinical treatment rheumatic arthritis, rheumatoid arthritis.And the compound saussurea involucrata capsule effect obviously is better than FUFANG XUELIAN JIAONANG.
Two, compound saussurea involucrata capsule and compound saussurea involucrata hard capsule dissolution are relatively
1 experiment material
1.1 instrument UV-2401 ultraviolet-visible spectrophotometer (day island proper Tianjin); 1100 high performance liquid chromatographs (Agilent); Chromatographic column Shimadzu VP-ODS (150L * 4.6,5 μ m); Chromatographic column Agilent ZORBAX SB-C
18(4.6 * 250mm, 5 μ m); BP211D (d=0.01mg) precision balance (German Sartorius); ZRS-8G intelligence digestion instrument (Radio Factory of Tianjin Univ.).
1.2 medicine and reagent compound saussurea involucrata capsule (Tefeng Pharmaceutical Co Ltd, Xinjiang's development, lot number: 20030924); FUFANG XUELIAN JIAONANG (the accurate word Z65020059 of traditional Chinese medicines, Xinjiang Chinese medicine head factory is produced, lot number 031020); Control substance of Rutin (lot number; 0080-9705); Methanol, acetonitrile are chromatographically pure; Water is distilled water; Other reagent etc. is analytical pure.
2 methods and result
The three therapeutic methods of traditional Chinese medicine is carried out under dissolution determination employing Chinese Pharmacopoeia version dissolution determination in 2000 item, rotating speed 50r/min is a medium with pure water 150mL, and temperature is 37 ± 0.5 ℃, sampling time point is 5,15,30,45,60,90,120,150min, sampling amount 2ml.Replenish equality of temperature fresh medium 2ml after each sampling immediately, sample is immediately through 0.8 μ m filtering with microporous membrane, essence is got subsequent filtrate 50 μ L, measure the content of rutin, calculate the accumulation stripping percentage rate of every medicine, the result sees table 5 for details, Figure of description: compound saussurea involucrata hard capsule and soft capsule stripping curve figure.
Table 5. is at average accumulated stripping percentage rate (%, X ± S) (n=6) of different time
Time (min)
15 30 45 60 90 120 150
Hard capsule 22.67 ± 9.77 37.73 ± 7.49 53.13 ± 9.65 58.23 ± 6.33 70.32 ± 7.58 75.81 ± 5.13 80.25 ± 4.59
Soft capsule 49.74 ± 13.99 62.34 ± 9.23 67.03 ± 8.22 70.59 ± 6.59 73.06 ± 7.71 79.39 ± 8.35 86.61 ± 11.6
3 date processing
According to Weibull (Weibull) distribution function,,, extract stripping parameter m, T with Casio fx-3600pv computer fitting a straight line to accumulation stripping percentage rate
50, T
d, the stripping parameter is done the t check, the result sees table 3 for details.
The stripping parameter of table 3. compound saussurea involucrata capsule and hard capsule (X ± S) (n=6)
m T
50 T
d
Hard capsule 0.83 ± 0.20 48.24 ± 11.81 75.23 ± 15.80
Soft capsule 0.46 ± 0.07 18.6 ± 10.84 40.78 ± 22.20
P ＜0.05 ＜0.05 ＜0.05
As a result, compound saussurea involucrata hard capsule and soft capsule stripping parameter m, T
50, T
dThrough variance analysis, has significant difference.
4 discuss
Experimental result shows, the dissolution of compound saussurea involucrata capsule is faster than hard capsule, dependency according to bioavailability in dissolution in vitro and the body can be inferred, after FUFANG XUELIAN JIAONANG is made soft capsule, not only overcome shortcomings such as the easy moisture absorption of hard capsule dosage form, poor stability, and can improve the bioavailability of preparation.
Claims (12)
1, a kind of compound saussurea involucrata capsule Chinese medicine preparation is made up of capsule core material and softgel shell two parts, it is characterized in that capsule core material contains Chinese medicine extract and the volatile oil and the pharmaceutic adjuvant of effective dose, and pharmaceutic adjuvant comprises stabilizing agent, antioxidant, diluent; Softgel shell mainly is made up of gelatin and plasticizer, and contains antiseptic, pigment, correctives, screening agent and an amount of PEG400.
2, compound saussurea involucrata capsule according to claim 1, it is characterized in that described stabilizing agent is one or more in Cera Flava, Adeps caprae seu ovis, methylcellulose, ethyl cellulose, Polyethylene Glycol monostearate, tween 80, cetomacrogol 1000～6000, poloxamer 188～407, the glycerol.
3, compound saussurea involucrata capsule according to claim 1, it is characterized in that described antioxidant is one or more in vitamin E, tea polyphenols, tertiarybutylhydroquinone (TBHQ), Radix Glycyrrhizae antioxygen thing, Butylated hydroxyanisole (BHA), dibenzylatiooluene (BHT), the propyl gallate (PG).
4, compound saussurea involucrata capsule according to claim 1 is characterized in that, described diluent is one or more in Oleum Arachidis hypogaeae semen, Oleum Glycines, safflower oil, Oleum Hippophae, Oleum Camelliae, salad oil, PEG400, the corn wet goods.
5, compound saussurea involucrata capsule according to claim 1 is characterized in that, described plasticizer is one or more in glycerol, sorbitol, the sucrose.
6, compound saussurea involucrata capsule according to claim 1 is characterized in that, described antiseptic is one or more in methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, the butyl p-hydroxybenzoate.
7, compound saussurea involucrata capsule according to claim 1 is characterized in that, described pigment is lemon yellow, amaranth, carmine, cacao brown, white carbon black, in light green, greyish purple one or more.
8, compound saussurea involucrata capsule according to claim 1 is characterized in that, described correctives is one or more in bourbonal,ethyl vanillin, essential oil, the Mentholum.
9, compound saussurea involucrata capsule according to claim 1 is characterized in that, described screening agent is one or more in titanium dioxide, barium sulfate, ferrum oxide, the precipitated calcium carbonate.
10, compound saussurea involucrata capsule according to claim 1 is characterized in that the weight proportion of capsule core material component is:
The component percentage composition
Chinese medicine extract 10%～70%
The volatile oil corresponding amount
Stabilizing agent 0～20%
Antioxidant 0～2%
The diluent surplus
11, compound saussurea involucrata capsule according to claim 1 is characterized in that the weight proportion of softgel shell component is:
The component percentage composition
Gelatin 35%～45%
Plasticizer 18%～22%
Antiseptic 0.08%～0.11%
Pigment 0～1%
Correctives 0～0.1%
Screening agent 0～3%
PEG400 0～10%
Water surplus
12, compound saussurea involucrata capsule according to claim 1 preparation method, may further comprise the steps:
(1) extraction of Herba Saussureae Involueratae: amount takes by weighing the Herba Saussureae Involueratae that is up to the standards at first in accordance with regulations, added 8～12 times of 55～70% soak with ethanol 12 hours, reflux, extract, three times, each 1.5 hours, merge extractive liquid, filtered, decompression filtrate recycling ethanol, be condensed into thick paste or be dried to dried cream, be ground into the above fine powder of 80 orders, standby;
(2) extraction of 7 flavor Chinese medicines such as Rhizoma Corydalis: 7 flavor Chinese medicines such as Rhizoma Corydalis add 8～12 times of water gagings and soaked 12 hours, decoct twice each two hours, collecting decoction, filter, filtrate decompression is concentrated into 1: 1, and concentrated solution is measured 40% ethanol with 3 times and precipitated 24～48 hours under 5～25 ℃ of temperature or add to 95% edible ethanol that to contain alcoholic degree be 20～50% to precipitate and spend the night under 5～25 ℃ of temperature, get the supernatant decompression recycling ethanol, be condensed into thick paste or be dried to dried cream, be ground into the above fine powder of 80 orders, standby.Or 7 flavor Chinese medicines such as all the other Rhizoma Corydalis add 8～12 times of water gagings and soaked 0～12 hour, vapor distillation extracts volatile oil, distillation time 2～12 hours, extracting 1 time, collect volatile oil, aqueous solution after distillation device is in addition collected, and medicinal residues add 8～12 times of water gagings again and decocted 0.5～2 hour, filter, aqueous solution after filtrate and the distillation merges, filter, filtrate decompression is concentrated into 1: 1, and concentrated solution is measured 40% ethanol with 3 times and precipitated 24～48 hours under 5～25 ℃ of temperature or add to 95% edible ethanol that to contain alcoholic degree be 20～50% to precipitate and spend the night under 5～25 ℃ of temperature, get the supernatant decompression recycling ethanol, be condensed into thick paste or be dried to dried cream, be ground into the above fine powder of 80 orders, standby;
(3) capsule core material preparation: with above-mentioned two groups of equivalent extract mix homogeneously or with above-mentioned two groups of extract powder mix homogeneously, add volatile oil (or not adding), capsulation stabilizer, diluent, antioxidant, mix homogeneously is crossed colloid mill, and is standby;
(4) softgel shell preparation: water, plasticizer, PEG400 (or not adding), the antiseptic of aequum added to have in the interlayer stainless-steel pan that stirs decompressor stir, as first liquid; The gelatin of aequum is joined in the rustless steel jacketed pan that fills first liquid, and temperature is controlled at the room temperature stirring of constantly reducing pressure, and treats that gelatin grain expansion post-heating to 50～80 ℃ makes the gelatin grain all melt and dissolved; The screening agent, the pigment that add aequum under stirring continue decompression and stirred 30～120 minutes; Even melt and dissolved liquid filters, the filtrate insulation is left standstill or the degassing of reducing pressure stand-by;
(5) finished product preparation: it is poor that capsule core material is put into liquid storage, uses rotating mould platen press compacting soft capsule; Wash ball, drying then, be packaged to be compound saussurea involucrata capsule.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102335216A (en) * | 2010-07-14 | 2012-02-01 | 株式会社安露莎 | Inhibitor for generation of melanin |
| CN102511821A (en) * | 2011-12-30 | 2012-06-27 | 新疆医科大学 | Composite lipid-lowering soft capsule preparation prepared by lycopene and grapestone extracts and preparation method of composite lipid-lowering soft capsule preparation |
| CN106174559A (en) * | 2016-07-07 | 2016-12-07 | 海南正康药业有限公司 | A kind of soybean extract capsule |
| CN107468777A (en) * | 2017-08-01 | 2017-12-15 | 国药集团新疆制药有限公司 | FUFANG XUELIAN JIAONANG and preparation method thereof and device |
-
2004
- 2004-11-22 CN CNB2004100976392A patent/CN1321632C/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102335216A (en) * | 2010-07-14 | 2012-02-01 | 株式会社安露莎 | Inhibitor for generation of melanin |
| CN102511821A (en) * | 2011-12-30 | 2012-06-27 | 新疆医科大学 | Composite lipid-lowering soft capsule preparation prepared by lycopene and grapestone extracts and preparation method of composite lipid-lowering soft capsule preparation |
| CN102511821B (en) * | 2011-12-30 | 2013-10-02 | 新疆医科大学 | Composite lipid-lowering soft capsule preparation prepared by lycopene and grapestone extracts and preparation method of composite lipid-lowering soft capsule preparation |
| CN106174559A (en) * | 2016-07-07 | 2016-12-07 | 海南正康药业有限公司 | A kind of soybean extract capsule |
| CN107468777A (en) * | 2017-08-01 | 2017-12-15 | 国药集团新疆制药有限公司 | FUFANG XUELIAN JIAONANG and preparation method thereof and device |
| CN107468777B (en) * | 2017-08-01 | 2020-08-07 | 国药集团新疆制药有限公司 | Compound saussurea involucrata capsule and its preparation method and device |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1321632C (en) | 2007-06-20 |
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