CN1872212A - Microspheres in use for injection of Chinese traditional medicine of containing angelica, and preparation method - Google Patents
Microspheres in use for injection of Chinese traditional medicine of containing angelica, and preparation method Download PDFInfo
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- CN1872212A CN1872212A CNA2005100136784A CN200510013678A CN1872212A CN 1872212 A CN1872212 A CN 1872212A CN A2005100136784 A CNA2005100136784 A CN A2005100136784A CN 200510013678 A CN200510013678 A CN 200510013678A CN 1872212 A CN1872212 A CN 1872212A
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- angelicae sinensis
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- 239000003814 drug Substances 0.000 title claims description 31
- 238000002360 preparation method Methods 0.000 title claims description 23
- 238000002347 injection Methods 0.000 title abstract description 4
- 239000007924 injection Substances 0.000 title abstract description 4
- 244000061520 Angelica archangelica Species 0.000 title 1
- 235000001287 Guettarda speciosa Nutrition 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 26
- 244000179560 Prunella vulgaris Species 0.000 claims abstract description 3
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- 229940079593 drug Drugs 0.000 claims description 17
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- 238000001035 drying Methods 0.000 claims description 4
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- 239000012071 phase Substances 0.000 claims description 4
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 3
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- 239000011734 sodium Substances 0.000 claims description 3
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- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 claims description 3
- 238000000935 solvent evaporation Methods 0.000 claims description 3
- 244000037364 Cinnamomum aromaticum Species 0.000 claims description 2
- 235000014489 Cinnamomum aromaticum Nutrition 0.000 claims description 2
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- 229960004275 glycolic acid Drugs 0.000 claims description 2
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
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- 244000236658 Paeonia lactiflora Species 0.000 abstract description 5
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- 241000213006 Angelica dahurica Species 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 239000011806 microball Substances 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
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- 239000009188 angelicae sinensis extract Substances 0.000 description 4
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- 238000003809 water extraction Methods 0.000 description 3
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
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- YKRGDOXKVOZESV-WRJNSLSBSA-N Paeoniflorin Chemical group C([C@]12[C@H]3O[C@]4(O)C[C@](O3)([C@]1(C[C@@H]42)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)C)OC(=O)C1=CC=CC=C1 YKRGDOXKVOZESV-WRJNSLSBSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
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- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
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- YKRGDOXKVOZESV-UHFFFAOYSA-N paeoniflorin Natural products O1C(C)(C2(CC34)OC5C(C(O)C(O)C(CO)O5)O)CC3(O)OC1C24COC(=O)C1=CC=CC=C1 YKRGDOXKVOZESV-UHFFFAOYSA-N 0.000 description 2
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- ZRJBHWIHUMBLCN-SEQYCRGISA-N Huperzine A Natural products N1C(=O)C=CC2=C1C[C@H]1/C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-SEQYCRGISA-N 0.000 description 1
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- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
A microball for injection is prepared from 11 Chinese-medicinal materials including Chinese angelica root, Chuan-xiong rhizome, white peony root, prunella spike, etc, and high-molecular auxiliary. Its preparing process is also disclosed.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of Chinese medicine release injectable microsphere and preparation method thereof that contains Radix Angelicae Sinensis.
Background technology
The analgesic effect of the Radix Paeoniae Alba sees " herbal classic " the earliest, calls its " main pathogen stomachache ... pain relieving ".Modern pharmacological research confirms that also Radix Paeoniae Alba total glucosides mice intramuscular injection contained in the Radix Paeoniae Alba is the dose dependent analgesic activity, and the Radix Paeoniae hardship also has tangible analgesic effect.In addition, the Radix Paeoniae Alba also has many-sided pharmacological action, as calmness, spasmolytic, antiinflammatory, anti-stress or the like, makes it be widely used in various antalgesics.
The ejection preparation of relevant Chinese medicine is mainly freeze-dried powder all the time.But because the intravital half-life is shorter, make common oral formulations be faced with a series of problem, frequent as the clinical administration number of times, use inconvenience, patient's compliance (compliance) difference etc.
Inventor's process years of researches are found Chinese medicines such as Radix Angelicae Sinensis, the Radix Paeoniae Alba are made microsphere with suitable adjuvant after suitably extracting, and can reach non-lentamente constant release, reduce and take number of times, improve the purpose of patient's compliance.
Summary of the invention
The object of the invention has been to provide a kind of brand-new slow release, the injection Chinese medicine microsphere of high bioavailability.
Another object of the present invention is to provide the preparation method of this injectable microsphere.
The prescription of pharmaceutical composition of the present invention is (in a weight percentage):
Radix Angelicae Sinensis 4～9% Rhizoma Chuanxiongs 4～9% Radix Paeoniae Albas 2～8% Radix Rehmanniaes Preparata 2～8% Ramulus Uncariae Cum Unciss 10～15% Caulis Spatholobis 10～15% Spica Prunellaes 10～15% Semen Cassiaes 10～15% Concha Margaritiferas 10～15% Rhizoma Corydalis 4～9% Herba Asaris 0.5～2%.
Choosing prescription proportioning is (in a weight percentage):
Radix Angelicae Sinensis 6.75% Rhizoma Chuanxiong 6.75% Radix Paeoniae Alba 5.4% Radix Rehmanniae Preparata 5.4% Ramulus Uncariae Cum Uncis 13.5% Caulis Spatholobi 13.5% Spica Prunellae 13.5% Semen Cassiae 13.5% Concha Margaritifera 13.5% Rhizoma Corydalis 6.75% Herba Asari 1.34%.
Said medicine prescription proportioning is the weight proportion of institute's uses crude drug, need further process and suitable adjuvant be made microsphere described medical material if be made into preparation.
Can select that wherein independent the or mixed extraction of Radix Angelicae Sinensis, the Radix Paeoniae Alba, Rhizoma Chuanxiong medical material is processed into extract extracting method wherein and be selected from (but being not limited to this): decoction and alcohol sedimentation technique, ultrasonic extraction, supercritical extraction etc.
Method for optimizing is that the Radix Paeoniae Alba is extracted separately, with all the other medical material water extraction, concentrates the back ethanol precipitation, reclaims ethanol, gets drug extract; Perhaps, concentrate the back ethanol precipitation, reclaim ethanol, get drug extract the direct water extraction of all medical materials.
For the ease of understanding, existing extracting method with the Radix Paeoniae Alba, Rhizoma Chuanxiong and Radix Angelicae Sinensis three flavor medical materials is described below for example, but is not limited to this.
Radix Paeoniae Alba ultrasonic extraction: get white Peony Root, pulverize, add the water supersound extraction, concentrate Radix Paeoniae Alba extract.
Radix Paeoniae Alba alcohol extraction is followed the example of: get white Peony Root, pulverize, add alcohol reflux, concentrate and reclaim ethanol, continue to concentrate Radix Paeoniae Alba extract.
The Radix Angelicae Sinensis supercritical extraction: get the Radix Angelicae Sinensis medical material, felicity condition adopts down carbon dioxide supercritical fluid extraction, filter Radix Angelicae Sinensis extract.
The Radix Angelicae Sinensis water extraction adds resin method: the decocting in water ferment precipitate heating dissolved in distilled water of getting Radix Angelicae Sinensis, with calcium hydroxide saturated solution adjust pH, the placement sucking filtration that spends the night, filtrate is transferred pH5-6 with sulphuric acid, and ice is deposited and is spent the night, sucking filtration, filtrate is by the exchange of zwitterion hybrid resin, and exchange liquid is concentrated into certain volume, adds ethanol precipitation, ice is deposited the sucking filtration that spends the night, with pure hypostasis wave in ethanol and concentrate Radix Angelicae Sinensis extract.
Radix Angelicae Sinensis distillation and extraction method: take by weighing Radix Angelicae Sinensis powder in flask, with the distilled water lixiviate that refluxes, then under certain condition with raw material and immersion, distilling under reduced pressure, get the Radix Angelicae Sinensis distillate, add an amount of NaCl standing demix then, spill funnel Radix Angelicae Sinensis volatile oil is isolated with dividing, concentrate Radix Angelicae Sinensis extract.
Rhizoma Chuanxiong ethanol adds resin method: get the Rhizoma Chuanxiong decoction pieces, pulverize, ethanol is reflux, extract, in Soxhlet reflux, extract, device, sucking filtration, sucking filtration liquid is evaporated to dried, adds suitable quantity of water again, and heating makes dissolving, filter, filtrate is added on the macroporous resin column of having handled well, first water eluting, reuse ethanol elution, after reclaiming ethanol, continue to concentrate Rhizoma Chuanxiong extract.
The Rhizoma Chuanxiong ethanol extraction method: get the Rhizoma Chuanxiong medical material, suitably pulverize, add the ethanol extraction several times, merge extractive liquid, filters, and reclaims ethanol, concentrate Rhizoma Chuanxiong extract.
Except that the independent extraction of above-mentioned medical material, all right mixed extraction of described Rhizoma Chuanxiong, Radix Angelicae Sinensis and the Radix Paeoniae Alba is mainly: the Radix Paeoniae Alba, Rhizoma Chuanxiong and the Radix Angelicae Sinensis medical material of learning from else's experience and pulverizing, and boiling water boils to be carried, filter, merging filtrate, and filtrate is suitably concentrated; Add ethanol and carry out precipitate with ethanol in concentrated solution, leave standstill, supernatant reclaims ethanol, is condensed into extractum, gets medicinal substances extract.
Injectable microsphere diameter of the present invention is 1～250 μ m, is made up of at 5000～1000000 daltonian biodegradable medical high-molecular additives the active component of microsphere gross weight 0.2%～50% (w/w) and the molecular weight of derivant and microsphere gross weight 50～99.8% (w/w) thereof.Wherein said biodegradable medical high-molecular additive is selected from wherein a kind of of polylactide, Acetic acid, hydroxy-, bimol. cyclic ester, polylactic acid, polyglycolic acid, poly--the 3-butyric ester, polylactic acid-polyglycolic acid, polylactic acid, glycolic, poly-adjacent ester, polylactone, polyanhydride, poly butyric ester-hydroxyl pentanoate copolymer, polyglycolic acid, polypropylene glucosan, hydroxyacetic acid, polylactic acid-polyglycol, polyglycolic acid, Polyethylene Glycol; Preferred polylactide-co-glycolide, polylactic acid, polylactic acid, polyglycolic acid, polylactic acid, glycolic, poly butyric ester-hydroxyl pentanoate copolymer, the best is polylactide, Acetic acid, hydroxy-, bimol. cyclic ester, molecular weight is 12000～15000 dalton; The polymerization ratio of lactide-Acetic acid, hydroxy-, bimol. cyclic ester is 40: 60-60: 40.
Microsphere of the present invention can adopt the conventional preparation method of microsphere to make, as adopting emulsifying dispersion method, spray drying method and solvent evaporation method, preferably spray drying method.When preparing microsphere of the present invention with the emulsifying dispersion method, with dichloromethane, chloroform, ethyl acetate, dioxane, ether, acetone, oxolane, glacial acetic acid and by the mixed acid that they are formed huperzine A or derivatives thereof and the dissolving of biodegradable pharmaceutic adjuvant are mixed with organic facies, wherein the bulking value percent of pharmaceutic adjuvant in organic solvent is 1～30%, the emulsifying agent that organic facies adopts is the nonionic emulsifier of HBL=4.5～6.0, and consumption is the 0.01-12% of organic facies; Prepare continuous water with polyvinyl alcohol, polyvinyl pyrrolidone, sodium polymethacrylate, sodium polyacrylate, sodium carboxymethyl cellulose solution in addition, wherein they are 0.01～10.0% in the percetage by weight of aqueous phase, the emulsifying agent of aqueous phase is the nonionic emulsifier of HLB=14.0～15.5, and consumption is 0.01～12% of a water; The volume ratio of organic facies and water is 1: 4～100; Organic facies slowly is injected in the continuous phase by tubule, fully emulsified after, the formed microsphere of sieving separating is drying to obtain.When adopting solvent evaporation method, be decentralized photo slowly be injected into by tubule in the continuous phase fully emulsified after, the decompression solvent flashing, centrifugalize obtains formed microsphere, is drying to obtain.
When adopting the spray drying method for preparation microsphere, to be the mixed acid formed with dichloromethane, chloroform, ethyl acetate, dioxane, ether, acetone, oxolane, glacial acetic acid and by them Chinese medicine extract and biodegradable pharmaceutic adjuvant fully dissolve is mixed with organic solution; Filter, spray drying is made microsphere.
Microsphere of the present invention be will make microsphere sterilized powder suspendible in aseptic 0.9% normal saline solvent earlier, evenly the back intramuscular injection comes administration.
In motherland's medical science to record that pill has " the ball person is slow also, releives and controls it ... " (Li Gao, 1180-1251).As seen Ancient Times in China medicine man early has recognized that and has used practice of pharmacy, reaches the purpose of steadily lasting curative effect.
Conventional dosage forms, most drug release process is all undertaken by first order kinetics, and the blood drug level of its medicine might be lower than minimum effective blood drug concentration and hold time short shortcoming in treatment concentration.For reaching therapeutic purposes and reducing side effect and often take repeatedly medicining mode, the compliance that makes the patient take medicine like this descends.Slow releasing preparation has overcome the deficiency of conventional formulation just, and steady, persistent blood drug level is provided.
Chinese medicine microsphere of the present invention has adopted the design principle of Western medicine slow releasing preparation to obtain achievement at aspects such as adjuvant selection, quality evaluations, for the research of Chinese medicine slow releasing preparation is used for reference.
Below beneficial effect by extracorporeal releasing test explanation microsphere
Laboratory sample: according to the microsphere of the embodiment of the invention 1,2,3 described method preparations.
Experiment reagent: the buffer solution (4.0,5.5) of certain pH value.
Experimental apparatus: constant temperature oscillator, centrifuge.
Experiment condition: temperature: 37 ± 10 ℃; Rotating speed: 30rp/ minute.
Experimental technique: precision takes by weighing the about 10mg of laboratory sample, and to place volume be the tool lid plastic centrifuge tube of 15ml, adds 5ml release medium (PH=4.0 and 5.5 phosphate buffer solutions) and place constant temperature oscillator, keeps certain temperature and rotating speed to take a sample on time.
Sampling method: centrifugal 50min under the 3600 commentaries on classics conditions, essence is got 3ml solution, adds the release medium of 3ml again, takes out liquid and detects with HPLC.Concrete detection index is a paeoniflorin, detects wavelength: 281nm.
Sampling time point (my god): 0,1,2,4,6,8,10,12,14,16,18,20.
Result of the test: the external release test of control-release microsphere is table 1 as a result.
Paeoniflorin release in vitro result in table 1, the microsphere
| Sample | The PH value | Value mode | Discharge percent (%) | |||||||||||
| 0 | 1 | 2 | 4 | 6 | 8 | 10 | 12 | 14 | 16 | 18 | 20 | |||
| Embodiment | 4.0 | The same day | 0 | 26.6 | 4.0 | 0 | 1.5 | 1.13 | 14.0 | 12.00 | 3.0 | 0 | 6.5 | |
| Accumulation | 0 | 26.6 | 30.6 | 30.6 | 33.6 | 35.9 | 64.0 | 90.8 | 93.8 | 93.8 | 106.8 | 106.8 | ||
| Example 1 | 5.5 | The same day | 0 | 28.0 | 2.0 | 2.0 | 1.5 | 1.7 | 29.5 | 16.4 | 1.0 | 0 | 0.5 | |
| Accumulation | 0 | 28.0 | 30.0 | 30.0 | 33 | 36.4 | 95.4 | 128.2 | 130.2 | 130.2 | 131.2 | 131.2 | ||
| Embodiment 2 | 4.0 | The same day | 0 | 28.3 | 0.3 | 0.3 | 1.1 | 2.1 | 9.0 | 11.35 | 4.8 | 2.8 | 0.85 | 0.5 |
| Accumulation | 0 | 28.3 | 28.6 | 28.6 | 32.7 | 36.9 | 54.9 | 79.6 | 89.2 | 94.8 | 96.5 | 97.5 | ||
| 5.5 | The same day | 0 | 18.1 | 0.9 | 0.9 | 0.05 | 2.65 | 8.6 | 10.5 | 12.7 | 2.05 | 1.2 | 0.6 | |
| Accumulation | 0 | 18.1 | 19.0 | 19.0 | 26.1 | 31.4 | 48.6 | 69.6 | 95.0 | 99.1 | 101.5 | 102.7 | ||
| Embodiment 3 | 4.0 | The same day | 0 | 33.8 | 2.1 | 2.1 | 2.5 | 3.0 | 5.95 | 11.65 | 5.05 | 1.2 | 0.45 | 0.35 |
| Accumulation | 0 | 33.8 | 35.9 | 35.9 | 42.5 | 49.5 | 61.4 | 84.7 | 94.8 | 97.2 | 98.1 | 98.8 | ||
| 5.5 | The same day | 0 | 31.7 | 1.7 | 1.7 | 1.3 | 2.35 | 17.65 | 4.2 | 5.75 | 1.15 | 0.55 | 0.2 | |
| Accumulation | 0 | 31.7 | 33.4 | 33.4 | 39.9 | 44.6 | 79.9 | 88.3 | 99.8 | 102.1 | 103.2 | 103.6 |
The specific embodiment
The present invention is further illustrated below in conjunction with embodiment, and following this embodiment only is used to the present invention is described and to the present invention without limits.
Embodiment 1
Take off and state medical material: Radix Angelicae Sinensis 80g, Rhizoma Chuanxiong 80g, Radix Paeoniae Alba 80g, Radix Rehmanniae Preparata 80g, Ramulus Uncariae Cum Uncis 120g, Caulis Spatholobi 120g, Spica Prunellae 120g, Semen Cassiae 120g, Concha Margaritifera 120g, Rhizoma Corydalis 70g, Herba Asari 10g;
The extraction of the Radix Paeoniae Alba: get above-mentioned white Peony Root 80g, crushing screening adds the water supersound extraction 2 times, for the first time make a living 10 times of dose of amount of water volume, supersonic frequency is 5MHz, time is 50min, is extracted as 8 times of crude drug amount for the second time, and supersonic frequency is 5Mhz, time is 40min, merge extractive liquid, concentrates, and gets Radix Paeoniae Alba extract.
The extraction of other medical material: above-mentioned other medical material mix homogeneously, extracting in water 2 times, for the first time amount of water is 8 times of crude drug, 2 hours extraction times, 6 times of the dose of making a living for the second time, 1.5 hours extraction times, merge extractive liquid,, being concentrated into relative density is 1.10 (W/W), gets medicinal substances extract.
The preparation of microsphere: above-mentioned 100mg extract, 200mg polylactide-co-glycolide are dissolved in the 3ml dichloromethane, with syringe under high degree of agitation with it to being equipped with in the three-necked bottle of 10%PVA that 300ml includes the 3.5Ghlb=14 emulsifying agent, after fully emulsified 1 hour, under the pressure of 30 ℃ of 0.03MPa, solvent flashing 1.5 hours, centrifugalize, wash reactant three times with distillation, in 30 ℃ of vacuum drying ovens, dry, sterilized 48 hours at 30 ℃ with oxirane, guarantee residual ethylene oxide content below 5ppm, fill.
Embodiment 2
Take off and state medical material: Radix Angelicae Sinensis 80g, Rhizoma Chuanxiong 80g, Radix Paeoniae Alba 80g, Radix Rehmanniae Preparata 80g, Ramulus Uncariae Cum Uncis 120g, Caulis Spatholobi 120g, Spica Prunellae 120g, Semen Cassiae 120g, Concha Margaritifera 120g, Rhizoma Corydalis 70g, Herba Asari 10g;
The extraction of white Peony Root: get Radix Paeoniae Alba crude drug, pulverize, cross 120 mesh sieves, the alcohol reflux of adding 80% 2 times, make a living for the first time 8 times of dose, 5 times of the doses of making a living for the second time extracted respectively 2 hours and 1 hour, merge extractive liquid,, standing over night filters centrifugal (12000r/min) after-filtration, reclaim ethanol, continue the concentrated Radix Paeoniae Alba extract that obtains.
The extraction of other medical material: above-mentioned other medical material mix homogeneously, extracting in water 2 times, for the first time amount of water is 8 times of crude drug, 2 hours extraction times, 6 times of the dose of making a living for the second time, 1.5 hours extraction times, merge extractive liquid,, being concentrated into relative density is 1.10 (W/W), gets medicinal substances extract.
The preparation of microsphere: above-mentioned 100mg extract, 200mg polylactide-co-glycolide are dissolved in the 3ml dichloromethane, with syringe under high degree of agitation with it to being equipped with in the three-necked bottle of 10%PVA that 300ml includes the 3.5Ghlb=14 emulsifying agent, after fully emulsified 1 hour, under the pressure of 30 ℃ of 0.03MPa, solvent flashing 1.5 hours, centrifugalize, wash reactant three times with distillation, in 30 ℃ of vacuum drying ovens, dry, sterilized 48 hours at 30 ℃ with oxirane, guarantee residual ethylene oxide content below 5ppm, fill.
Embodiment 3
Take off and state medical material: Radix Angelicae Sinensis 67.5g, Rhizoma Chuanxiong 67.5g, Radix Paeoniae Alba 54g, Radix Rehmanniae Preparata 54g, Ramulus Uncariae Cum Uncis 135g, Caulis Spatholobi 135g, Spica Prunellae 135g, Semen Cassiae 135g, Concha Margaritifera 135g, Rhizoma Corydalis 67.5g, Herba Asari 14.5g;
The extraction of Rhizoma Chuanxiong: getting 67.5g Rhizoma Chuanxiong medical material, with 8 times of 70% alcohol reflux 3 times, is 2 hours for the first time and for the second time, is 1.5 hours for the third time, and merge extractive liquid, filters, and reclaims ethanol, continue to concentrate Rhizoma Chuanxiong extract.
The extraction of other medical material: above-mentioned other medical material mix homogeneously, extracting in water 2 times, for the first time amount of water is 8 times of crude drug, 2 hours extraction times, 6 times of the dose of making a living for the second time, 1.5 hours extraction times, merge extractive liquid,, being concentrated into relative density is 1.10 (W/W), gets medicinal substances extract.
The preparation of microsphere: take by weighing the above-mentioned extract 100mg that obtains, polylactide-co-glycolide (lactide: Acetic acid, hydroxy-, bimol. cyclic ester=50: 50), 2.0g in small beaker, the 31.5ml that adds methylene chloride, electromagnetic agitation is used filtering with microporous membrane to fully dissolving, adopt the spray drying method for preparation microsphere, record particle diameter 5～80gm, sterilization, packing.
Embodiment 4
Take off and state medical material: Radix Angelicae Sinensis 67.5g, Rhizoma Chuanxiong 67.5g, Radix Paeoniae Alba 54g, Radix Rehmanniae Preparata 54g, Ramulus Uncariae Cum Uncis 135g, Caulis Spatholobi 135g, Spica Prunellae 135g, Semen Cassiae 135g, Concha Margaritifera 135g, Rhizoma Corydalis 67.5g, Herba Asari 14.5g;
The extraction of Rhizoma Chuanxiong medical material: get Rhizoma Chuanxiong medical material 67.5g, pulverize slightly, with 95% ethanol in Soxhlet reflux, extract, dress and middle reflux, extract, 9 hours: the solvent consumption is 8-10 times.Extracting solution is taken out turbid device sucking filtration with Bu Shi, sucking filtration liquid concentrating under reduced pressure as for, add suitable quantity of water again, heating makes dissolving, sucking filtration, filtrate is added on the macroporous resin column of having handled well (ratio of dried cream and resin is 1: 15), water elution, reuse 70% ethanol elution is collected eluent, reclaim ethanol, continue to concentrate Rhizoma Chuanxiong extract.
The extraction of other medical material: above-mentioned other medical material mix homogeneously, extracting in water 2 times, for the first time amount of water is 8 times of crude drug, 2 hours extraction times, 6 times of the dose of making a living for the second time, 1.5 hours extraction times, merge extractive liquid,, being concentrated into relative density is 1.10 (W/W), gets medicinal substances extract.
The preparation of microsphere: take by weighing and get above-mentioned extract 100mg (ratio is 1: 1) altogether, polylactide-co-glycolide (lactide: Acetic acid, hydroxy-, bimol. cyclic ester=60: 40), 4.0g in small beaker, the 41ml that adds methylene chloride, electromagnetic agitation adopts the spray drying method for preparation microsphere to fully dissolving, record particle diameter 1～50 μ m, mean diameter 13.26 μ m, sterilization, packing.
Embodiment 5
Take off and state medical material: Radix Angelicae Sinensis 67.5g, Rhizoma Chuanxiong 67.5g, Radix Paeoniae Alba 54g, Radix Rehmanniae Preparata 54g, Ramulus Uncariae Cum Uncis 135g, Caulis Spatholobi 135g, Spica Prunellae 135g, Semen Cassiae 135g, Concha Margaritifera 135g, Rhizoma Corydalis 67.5g, Herba Asari 14.5g;
The extraction of Radix Angelicae Sinensis medical material: take by weighing Radix Angelicae Sinensis powder 67.5g in flask, behind the bloated 24h (room temperature) of distilled water preimpregnation, lixiviate (soaking but the electricity consumption stirring helps) refluxes, then with raw material and immersion at (50-60) ℃, 0.09MPa under the condition, distilling under reduced pressure, the flow velocity of distillate (2-3) mL/min, distillate be about stop four of lixiviating solution/a period of time the distillation.Add the NaCl standing demix be equivalent to distillate quality 10% then, concentrate Radix Angelicae Sinensis extract.
The extraction of other medical material: above-mentioned other medical material mix homogeneously, extracting in water 2 times, for the first time amount of water is 8 times of crude drug, 2 hours extraction times, 6 times of the dose of making a living for the second time, 1.5 hours extraction times, merge extractive liquid,, being concentrated into relative density is 1.10 (W/W), gets medicinal substances extract.
The preparation of microsphere: with extract 100mg, (lactide: Acetic acid, hydroxy-, bimol. cyclic ester=50: 50) 1.0g places small beaker to polylactide-co-glycolide altogether, adds glacial acetic acid 22ml, electromagnetic agitation adopts the spray drying method for preparation microsphere to fully dissolving, records particle diameter 1～100 μ m, sterilization, packing.
Claims (10)
1. one kind contains the Radix Angelicae Sinensis sustained-release micro-spheres, comprise that 0.2～50% the extract by Chinese crude drug is that 50～99.8% molecular weight ranges of active component and microsphere weight is 5,000～1,000, biodegradable medicinal high polymer adjuvant between 000 is formed, and the composition of its Chinese crude drug is by weight ratio: Radix Angelicae Sinensis 4～9% Rhizoma Chuanxiongs 4～9% Radix Paeoniae Albas 2～8% Radix Rehmanniaes Preparata 2～8% Ramulus Uncariae Cum Unciss 10～15% Caulis Spatholobis 10～15% Spica Prunellaes 10～15% Semen Cassiaes 10～15% Concha Margaritiferas 10～15% Rhizoma Corydalis 4～9% Herba Asaris 0.5～2%
2. the described microsphere of claim 1, wherein said medicinal high polymer adjuvant are selected from polylactide-co-glycolide, polylactic acid, polyglycolic acid, poly--the 3-butyric ester, polylactic acid-polyglycolic acid, polylactic acid. glycolic, poly-adjacent ester, polylactone, polyanhydride, poly butyric ester-hydroxyl pentanoate copolymer, polyglycolic acid, polypropylene glucosan, hydroxyacetic acid, polylactic acid-polyglycol, polyglycolic acid. and Polyethylene Glycol a kind of or two or more mixing wherein wherein.
3. the described microsphere of claim 1, wherein said medicinal high polymer adjuvant is selected from polylactide-co-glycolide, polylactic acid, polylactic acid. wherein a kind of of polyglycolic acid, polylactic acid-glycollic acid, poly butyric ester-hydroxyl pentanoate copolymer or two or more mixing wherein.
4. the described microsphere of claim 1, wherein medicinal high polymer adjuvant is a polylactide-co-glycolide.
5. the described microsphere of claim 1, its molecular weight of wherein said polylactide-co-glycolide is between 12000～15000 dalton.
6. the described microsphere of claim 1, wherein in the polylactide-co-glycolide lactide and Acetic acid, hydroxy-, bimol. cyclic ester polymerization ratio between 40: 60～60: 40.
7. the described microsphere of claim 1, the weight percentage of active component crude drug wherein is: Radix Angelicae Sinensis 6.75% Rhizoma Chuanxiong 6.75% Radix Paeoniae Alba 5.4% Radix Rehmanniae Preparata 5.4% Ramulus Uncariae Cum Uncis 13.5% Caulis Spatholobi 13.5% Spica Prunellae 13.5% Semen Cassiae 13.5% Concha Margaritifera 13.5% Rhizoma Corydalis 6.75% Herba Asari 1.34%.
8. the preparation method of the described microsphere of claim 1, it is to adopt the emulsifying dispersion method to make, it is characterized in that using dichloromethane, chloroform, ethyl acetate, dioxane, ether, acetone, oxolane, glacial acetic acid and the mixed acid be made up of them are medicinal substances extract and the dissolving of biodegradable pharmaceutic adjuvant, wherein the bulking value percent of pharmaceutic adjuvant in organic solvent is 1～30%, the emulsifying agent that organic facies adopts is the nonionic emulsifier of HLB=4.5～6.0, uses polyvinyl alcohol, polyvinyl pyrrolidone, consumption is 0.01～12% of an organic facies; Sodium polymethacrylate, sodium polyacrylate, sodium carboxymethyl cellulose solution in addition, prepare continuous water, wherein they are 0.01～10.0 in the percetage by weight of aqueous phase, and the emulsifying agent of aqueous phase is the nonionic emulsifier of HLB=14.0～15.5, and consumption is 0.01～12% of a water; Decentralized photo slowly is injected in the continuous phase by tubule, and emulsifying is sieved then, is drying to obtain.
9. the preparation method of the described microsphere of claim 1, it is to adopt solvent evaporation method to make, the mixed acid that it is characterized in that forming with dichloromethane, chloroform, ethyl acetate, dioxane, ether, acetone, oxolane, glacial acetic acid and by them is medicinal substances extract and the dissolving of biodegradable pharmaceutic adjuvant, wherein the bulking value percent of pharmaceutic adjuvant in organic solvent is 1～30%, the emulsifying agent that organic facies adopts is the nonionic emulsifier of HLB=4.5～6.0, and consumption is 0.01～12% of an organic facies; Use polyvinyl alcohol, polyvinyl pyrrolidone, sodium polymethacrylate, sodium polyacrylate, sodium carboxymethyl cellulose solution in addition, prepare continuous water, wherein they are 0.01～10.0 in the percetage by weight of aqueous phase, the emulsifying agent of aqueous phase is the nonionic emulsifier of HLB=14.0～15.5, and consumption is 0.01～12% of a water; Decentralized photo slowly is injected in the continuous phase by tubule, fully emulsified, the solvent flashing that reduces pressure then, centrifugalize is drying to obtain.
10. the preparation method of the described microsphere of claim 1, it is to adopt spray drying method to make, the molecular weight that it is characterized in that mixed-acid dissolution 0.2～50% medicinal substances extract formed with dichloromethane, chloroform, ethyl acetate, dioxane, ether, acetone, oxolane, glacial acetic acid and by them and derivant and 50～99.8% is at 5000～1000000 daltonian biodegradable medical high-molecular additives, after stirring fully dissolving, filter, adopt spray drying method to make microsphere.
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| CNA2005100136784A CN1872212A (en) | 2005-06-03 | 2005-06-03 | Microspheres in use for injection of Chinese traditional medicine of containing angelica, and preparation method |
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| CNA2005100136784A CN1872212A (en) | 2005-06-03 | 2005-06-03 | Microspheres in use for injection of Chinese traditional medicine of containing angelica, and preparation method |
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