CN102198209B - Tendon-relaxing and blood-activating capsules and preparation process thereof - Google Patents

Tendon-relaxing and blood-activating capsules and preparation process thereof Download PDF

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CN102198209B
CN102198209B CN 201110129493 CN201110129493A CN102198209B CN 102198209 B CN102198209 B CN 102198209B CN 201110129493 CN201110129493 CN 201110129493 CN 201110129493 A CN201110129493 A CN 201110129493A CN 102198209 B CN102198209 B CN 102198209B
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王维
周建仁
彭腊梅
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Zhejiang Kangrun Pharmaceutical Co ltd
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HANGZHOU HUADONG PHARMACEUTICAL GROUP KANGRUN PHARMACEUTICAL CO Ltd
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Abstract

The invention discloses tendon-relaxing and blood-activating capsules and a preparation process thereof. In the invention, through the improvement on the preparation process, the active ingredient content in the tendon-relaxing and blood-activating capsules is improved and the bioavailability is improved, so the dosage is reduced. The extraction method disclosed by the invention is simple and convenient and is favorable for industrial production.

Description

A kind of tendon-relaxing blood circulation-activating capsule and preparation technology thereof
Technical field
The invention belongs to Chinese medicine preparation, relate generally to a kind of tendon-relaxing blood circulation-activating capsule and preparation technology thereof.
Background technology
Tablet for relieving rigidity of muscles and promoting blood circulation records in " Drug Standard of Ministry of Public Health of the Peoples Republic of China " the 13 in preparation of Chinese traditional patent formulation (hereinafter to be referred as standard), belongs to national essential drugs and medical insurance catalogue kind.Tablet for relieving rigidity of muscles and promoting blood circulation is because manufacturer is numerous, and product quality is uneven; On technology, adopt directly to pulverize with part water and carry the back preparation, the tablet formulation process need add some kinds of adjuvant compression formings, exists disintegration time long, and stripping is slow, dose shortcomings such as (3 times on the one, a time 5) and bioavailability be low greatly.
The described preparation technology of patent No. CN1883635A " tendon-relaxing blood circulation-activating capsule and preparation method thereof " is consistent with the technology of the tablet for relieving rigidity of muscles and promoting blood circulation tablet of standard promulgation.And the stripping to active ingredient does not make a search, and has shortcomings such as consumption big (3 times on the one, a time 5) and bioavailability are low equally.
Patent No. CN1362123A " nanometer relaxing muscles and tendons to promote blood circulation preparation medicine and preparation method thereof " adopts nanotechnology with the medical material nanorize, innovation to some extent technically, but apparatus expensive that should technology, and production cost is very high, is not suitable for suitability for industrialized production and application.
Summary of the invention
Technological deficiency such as the object of the invention overcomes prolonged disintegration in the prior art, dose is big and bioavailability is low provides a kind of tendon-relaxing blood circulation-activating capsule efficiently.
The invention discloses a kind of tendon-relaxing blood circulation-activating capsule, form by the raw material of following weight parts:
35 parts on Flos Carthami, 132 parts of Rhizoma Cyperis (system), 175 parts of Rhizoma Cibotii (system), 87 parts of Cortex Periplocaes, 132 parts of Caulis Trachelospermis, 132 parts of Herba Lycopodiis, 132 parts of herba lycopis, 175 parts of Herba Viscis, 132 parts of Caulis Spatholobis, 22 parts of Pyritums (forging); This tendon-relaxing blood circulation-activating capsule disclosed by the invention is to make through following preparation process:
A, Pyritum (forging) decocte with water 2 hours are filtered, and be subsequent use;
B, Flos Carthami, Rhizoma Cyperi (system), Rhizoma Cibotii (system), Cortex Periplocae, Caulis Trachelospermi, Herba Lycopodii, herba lycopi, Herba Visci, Caulis Spatholobi are ground into fine powder, sieve, and the adding pH value is 1~10 ethanol; Under slight boiling condition, extract 2 times; 2 hours for the first time, 1 hour for the second time, filter;
C, three filtratings of merging are concentrated into thick paste, spray drying;
D, sieve, incapsulate.
Wherein among the step b, institute adds alcoholic acid pH value, is 2 when extracting for the first time, is 9 when extracting for the second time; To add ethanol be that concentration is the ethanol of 40-80%, be preferably concentration and be 60% ethanol; Institute adds alcoholic acid amount, by solid-to-liquid ratio, is 1: 6~10 (g/ml), is preferably 1: 8 (g/ml).
Wherein among the step c, spray-dired intake air temperature is 170 ℃; The air outlet temperature is 95 ℃.
The invention also discloses a kind of method for preparing tendon-relaxing blood circulation-activating capsule, comprise following preparation process:
A, Pyritum decocte with water 2 hours are filtered, and be subsequent use;
B, Flos Carthami, Rhizoma Cyperi, Rhizoma Cibotii, Cortex Periplocae, Caulis Trachelospermi, Herba Lycopodii, herba lycopi, Herba Visci, Caulis Spatholobi are ground into fine powder, sieve, and the adding pH value is 1~10 ethanol, under slight boiling condition, extract 2 times, 2 hours for the first time, 1 hour for the second time, filter;
C, three filtratings of merging are concentrated into thick paste, spray drying;
D, sieve, incapsulate.
Wherein among the step b, institute adds alcoholic acid pH value, is 2 when extracting for the first time, is 9 when extracting for the second time; Add the ethanol that concentration of alcohol is 40-80%, be preferably concentration and be 60% ethanol; Institute adds alcoholic acid amount, by solid-to-liquid ratio, is 1: 6~10 (g/ml), is preferably 1: 8 (g/ml).
Wherein among the step c, spray-dired intake air temperature is 170 ℃; The air outlet temperature is 95 ℃.
The present invention improves extraction through adopting different control ethanol pH value, concentration, addition, makes to extract to have with short production cyclely, and production cost is low, and effective substance extracts more complete, and does not change advantage such as the original function of medicine.
The tendon-relaxing blood circulation-activating capsule that the present invention processes, through detecting, S-A Hydroxysafflor yellow A that is contained and tracheloside content obviously improve.Flos Carthami includes carthamone, neocarthamin, glycosides such as saffloside, and saffloside gets carthamin, glucose sugar and Flos Carthami flavochrome through acid hydrolysis.Hydroxy Carthamus yellow is the most effectively water soluble part of Flos Carthami pharmacological effect; Can suppress platelet aggregation and release that platelet activating factor brings out; Can suppress the combination of the platelet receptor that platelet activating factor brings out competitively, play the effect of blood circulation promoting and blood stasis dispelling.Caulis Trachelospermi obtains having the lignanoids extract of anti-inflammatory and analgesic effect through extraction, and tracheloside is wherein a kind of effective ingredient, has significant anti-inflammatory and antalgic activity, can be used for treating various inflammation and pain.Acid hydrolyzation makes the glycosides in the raw material be converted into aglycon and extracts in the lump, has improved the total content of active ingredient in product yield and the product greatly.
The tendon-relaxing blood circulation-activating capsule that the present invention makes improves the bioavailability of effective ingredient greatly, reduce dose (3 times on the one, a time 3), and its preparation technology is simple, is applicable to suitability for industrialized production.
The specific embodiment
Embodiment 1: extraction conditions research and test
1, pH value and extraction time are selected
(1) factor level is investigated
Pyritum 2.2g adds 10 times of water gagings earlier and decocted 2 hours.Flos Carthami 3.5g, Rhizoma Cyperi 13.2g, Rhizoma Cibotii 17.5g, Cortex Periplocae 8.7g, Caulis Trachelospermi 13.2g, Herba Lycopodii 13.2g, herba lycopi 13.2g, Herba Visci 17.5g, Caulis Spatholobi 13.2g; With acid extraction pH value, alkaline extraction pH value, acid extraction number of times, alkaline extraction number of times is the investigation factor; Each factor is selected 3 varying levels, and factor level is seen table 1.With S-A Hydroxysafflor yellow A content (mg/ grain) serves as to investigate index, confirms optimised process, does orthogonal test by L9 (34) table.
Table 1 factor level table
Figure BSA00000498792400031
(2) orthogonal test scheme and result
Table 2 orthogonal extraction testing program and table as a result
Figure BSA00000498792400032
Figure BSA00000498792400041
Can be known that by last table range analysis the A factor is maximum to the content influence of S-A Hydroxysafflor yellow A, promptly the acid extraction pH value has the greatest impact.A in the A factor 2>A 1>A 3, select best level A 2B in the B factor 2>B 1>B 3, select best level B 2C in the C factor 1>C 2>C 3, select best level C 1D in the D factor 1>D 2=D 3, select best level D 1Analysis result shows that optimised process consists of A 2B 2C 1D 1, promptly acid extraction once, pH value is 2; Alkaline extraction once, pH value is 9.
(3) orthogonal test variance analysis
Table 3 orthogonal extraction S-A Hydroxysafflor yellow A content analysis of variance table
Figure BSA00000498792400042
Wherein " * " is significant difference.The result learns from table 3: there were significant differences for the A factor (P<0.01), B, C, D there was no significant difference.That is: the acid extraction pH value has appreciable impact to S-A Hydroxysafflor yellow A content.
2, other factors are investigated
(1) the factor level condition is investigated
Pyritum 2.2g adds 10 times of water gagings earlier and decocted 2 hours.Flos Carthami 3.5g, Rhizoma Cyperi 13.2g, Rhizoma Cibotii 17.5g, Cortex Periplocae 8.7g, Caulis Trachelospermi 13.2g, Herba Lycopodii 13.2g, herba lycopi 13.2g, Herba Visci 17.5g, Caulis Spatholobi 13.2g; Extract twice, pH value is 2 for the first time, extracts 2 hours; PH value is 9 for the second time, extracts 1 hour.With ethanol volume fraction, solid-to-liquid ratio (doubly amount), acid extraction time, alkaline extraction time be the investigation factor, each factor is selected 3 varying levels, factor level is seen table 4.With S-A Hydroxysafflor yellow A content (mg/ grain) serves as to investigate index, confirms optimised process, presses L 9(3 4) table does orthogonal test.
Table 4 factor level table
Figure BSA00000498792400051
(2) orthogonal test scheme and result
Table 5 orthogonal extraction testing program and table as a result
Figure BSA00000498792400052
Can be known that by last table range analysis the A factor is maximum to the S-A Hydroxysafflor yellow A content influence, promptly ethanol volume fraction (%) has the greatest impact.A in the A factor 2>A 3>A 1, select best level A 2B in the B factor 2>B 3>B 1, select best level B 2C in the C factor 3>C 1>C 2, select best level C 3D in the D factor 1=D 2=D 3, select horizontal D from economic angle 1Analysis result shows that optimised process consists of A 2B 2C 3D 2, promptly get 60% ethanol, solid-to-liquid ratio 1: 8, extraction time is 120min for the first time, extraction time is 60min for the second time.
(3) orthogonal test variance analysis
Table 6 orthogonal extraction S-A Hydroxysafflor yellow A content analysis of variance table
Figure BSA00000498792400062
Wherein " * " is significant difference.The result learns from table 3: there were significant differences for the A factor (P<0.01), B, D there was no significant difference.That is: the ethanol volume fraction has appreciable impact to S-A Hydroxysafflor yellow A content.
Embodiment 2: the preparation tendon-relaxing blood circulation-activating capsule
Prescription: Flos Carthami 35g, Rhizoma Cyperi (system) 132g, Rhizoma Cibotii (system) 175g, Cortex Periplocae 87g, Caulis Trachelospermi 132g, Herba Lycopodii 132g, herba lycopi 132g, Herba Visci 175g, Caulis Spatholobi 132g, Pyritum (forging) 22g, dextrin is an amount of.
Method for making: Pyritum adds 10 times of water gagings and decocted 2 hours, filters, and is subsequent use.Flos Carthami, Rhizoma Cyperi, Rhizoma Cibotii, Cortex Periplocae, Caulis Trachelospermi, Herba Lycopodii, herba lycopi, Herba Visci, Caulis Spatholobi are ground into fine powder, cross sieve No. 5, add 8 times of amount pH value for the first time and be 2, concentration is extraction 2 hours 60% ethanol slight boiling condition under, emits a juice.Add for the second time 8 times of amount pH value and be 9, concentration is extraction 1 hour 60% ethanol slight boiling condition under, emits two juice.Merge filtrating three times, be concentrated into thick paste.Pump into spray drying in the spray dryer, intake air temperature: 170 ℃; Air outlet temperature: 95 ℃.Sieve, incapsulate, screen out the fine powder that invests the softgel shell surface with 16 order stainless steel sifts, polishing, packing promptly gets.The glue capsule is 1000 altogether.
Embodiment 3: tendon-relaxing blood circulation-activating capsule
Embodiment is said prepares according to patent " tendon-relaxing blood circulation-activating capsule and preparation method thereof " (patent No. 200610031734.1).Wherein raw material is: Flos Carthami 21g, Rhizoma Cyperi (system) 78.6g, Rhizoma Cibotii (system) 104.8g, Cortex Periplocae 52.4g, Caulis Trachelospermi 78.6g, Herba Lycopodii 78.6g, herba lycopi 78.6g, Herba Visci 104.8g, Caulis Spatholobi 78.6g, Pyritum (forging) 13.1g; Supplementary product starch 28~30g.
Preparation technology is: Flos Carthami, Rhizoma Cyperi, Rhizoma Cibotii, Cortex Periplocae are ground into fine powder, sieve; Pyritum adds 8 times of water gagings and decocted 2 hours, adds Caulis Trachelospermi, Herba Lycopodii, herba lycopi, Herba Visci, Caulis Spatholobi decoction secondary then, adds 12 times of water gagings 3 hours for the first time, adds 10 times of water gagings 2 hours for the second time; Collecting decoction filters, and leaves standstill, and the supernatant concentrating under reduced pressure becomes thick paste; Add above-mentioned powder 256g, add starch 28~30g, mixing is granulated; Drying, granulate is processed 1000.
Embodiment 4: contrast test
(1) S-A Hydroxysafflor yellow A (safflower effective ingredients) detection method of content
Chromatographic condition and system suitability experiment are filler with the octadecylsilane chemically bonded silica; With methanol-acetonitrile-0.2% phosphoric acid (16: 3: 81) is mobile phase; Flow velocity: 1.2ml/min; Column temperature: 25 ℃; The detection wavelength is 403nm.
It is an amount of that the S-A Hydroxysafflor yellow A reference substance is got in the preparation of reference substance solution, and accurate the title decides, and add methanol and process the solution that every 1ml contains 0.5mg, both.
The content under these article content uniformity item is got in the preparation of test liquid, mixing, and precision takes by weighing 1.0g, puts in the 100ml triangular flask; Accurate adding pH is 2 90% ethanol 50ml, claims to decide weight, puts ultrasonic echography 30min; Put coldly, claim decide weight again, and use pH is that 2 90% ethanol is supplied the weight that subtracts mistake; Shake up, filter, both.
Accurate respectively reference substance solution and the need testing solution 10ul of drawing of algoscopy injects chromatograph of liquid, measure, both.(2) tracheloside (Caulis Trachelospermi effective ingredient) detection method of content
Chromatographic condition and system suitability experiment are filler with the octadecylsilane chemically bonded silica; With acetonitrile: water (25: 75) is mobile phase; Flow velocity: 1.0ml/min; Column temperature: 28 ℃; The detection wavelength is 240nm.
It is an amount of that the tracheloside reference substance is got in the preparation of reference substance solution, and accurate the title decides, and add 25% acetonitrile and process the solution that every 1ml contains 0.4mg, both.
The content under these article content uniformity item is got in the preparation of test liquid, mixing, and precision takes by weighing 1.0g, puts in the 100ml round-bottomed flask; The accurate ethanol 50ml that adds claims to decide weight, to water-bath, refluxes 1 hour, adds water 500ml; Cross the AB-8 resin column of having handled well, 20% ethanol elution 1000ml collects 40% ethanol elution 500ml; And being concentrated into driedly, residue adds 10ml ethanol makes dissolving, both.
Accurate respectively reference substance solution and the need testing solution 10ul of drawing of algoscopy injects chromatograph of liquid, measure, both.
(3) disintegration detection method: press the Pharmacopoeia of the People's Republic of China 2010 editions, appendix X A inspection technique disintegration detects:
Get embodiment 2 and make medicine with embodiment 3, detect as stated above, the result is following:
Test item Embodiment 2 Embodiment 3
Hydroxy Carthamus yellow 0.55mg/ grain 0.38mg/ grain
Tracheloside 0.83mg/ grain 0.63mg/ grain
Disintegration (min) 10±2 13±2
Show from The above results, the tendon-relaxing blood circulation-activating capsule of the present invention's preparation, it obviously raises on S-A Hydroxysafflor yellow A and tracheloside content.The tendon-relaxing blood circulation-activating capsule of the present invention's preparation, disintegrate have short advantage of time.
Embodiment 5: the bioavailability test
Divide rat equally 2 groups at random, every group of 4 rats are on an empty stomach after 14 hours; Give embodiment 2 samples and embodiment 3 samples respectively and irritate stomach; Get blood respectively at 1h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 11h, 12h after the administration, with the centrifuge tube that blood sample places heparin sodium and sodium chloride to handle, centrifugal immediately; Separated plasma, be stored in-20 ℃ of refrigerators preserve to be measured.HPLC measures the S-A Hydroxysafflor yellow A blood drug level of different time in the rat body, draw S-A Hydroxysafflor yellow A at rat body medicine for parameter, like following table.
The bioavailability parameter Embodiment 2 Embodiment 3 Remarks
C max/ug?L -1 0.942±0.612 0.165±0.030 P<0.05
T 1/2/h 5.36±1.34 3.70±0.86 P<0.05
AUC 0→12(ug/L*h) 1.710±0.836 0.484±0.360 P<0.05
Show that from The above results the tendon-relaxing blood circulation-activating capsule bioavailability of the present invention's preparation obviously improves.

Claims (2)

1. tendon-relaxing blood circulation-activating capsule, by the raw material of following weight parts through preparing:
35 parts on Flos Carthami, 132 parts of Rhizoma Cyperi (processed), 175 parts of Rhizoma Cibotii of system, 87 parts of Cortex Periplocaes, 132 parts of Caulis Trachelospermis, 132 parts of Herba Lycopodiis, 132 parts of herba lycopis, 175 parts of Herba Viscis, 132 parts of Caulis Spatholobis, 22 parts of Pyritum (calcined)s;
Make through following preparation process:
A, Pyritum (calcined) decocte with water 2 hours are filtered, and be subsequent use;
B, Flos Carthami, Rhizoma Cyperi (processed), system Rhizoma Cibotii, Cortex Periplocae, Caulis Trachelospermi, Herba Lycopodii, herba lycopi, Herba Visci, Caulis Spatholobi are ground into fine powder, sieve, and adding concentration is 60% ethanol, under slight boiling condition, extracts 2 times; Wherein 2 hours for the first time, pH value was 2; 1 hour for the second time, pH value was 9, filtered; Wherein, add alcoholic acid amount and count 1: 8 by solid-to-liquid ratio;
C, three filtratings of merging are concentrated into thick paste, spray drying; Wherein spray-dired intake air temperature is 170 ℃, and the air outlet temperature is 95 ℃;
D, sieve, incapsulate.
2. method for preparing tendon-relaxing blood circulation-activating capsule as claimed in claim 1 comprises following preparation process:
A, Pyritum (calcined) decocte with water 2 hours are filtered, and be subsequent use;
B, Flos Carthami, Rhizoma Cyperi (processed), system Rhizoma Cibotii, Cortex Periplocae, Caulis Trachelospermi, Herba Lycopodii, herba lycopi, Herba Visci, Caulis Spatholobi are ground into fine powder, sieve, and adding concentration is 60% ethanol, under slight boiling condition, extracts 2 times; Wherein 2 hours for the first time, pH value was 2; 1 hour for the second time, pH value was 9, filtered; Wherein, add alcoholic acid amount and count 1: 8 by solid-to-liquid ratio;
C, three filtratings of merging are concentrated into thick paste, spray drying; Wherein spray-dired intake air temperature is 170 ℃, and the air outlet temperature is 95 ℃;
D, sieve, incapsulate.
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CN102652768A (en) * 2012-04-11 2012-09-05 南京同仁堂药业有限责任公司 Medicinal composition for relaxing tendons, activating collaterals, promoting blood circulation and removing blood stasis
CN110426469A (en) * 2019-08-02 2019-11-08 浙江工业大学 A kind of relaxing tendons and activating collaterals preparation finger and its application in total quality evaluation

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CN1883635A (en) * 2006-05-30 2006-12-27 湖南长沙宝鉴生物工程有限公司 Tendon-relaxing blood circulation-activating capsule and preparation process thereof

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Patentee before: Hangzhou Huadong Medicine Group Kangrun Pharmaceutical Co.,Ltd.