CN102772459A - In-situ gel for treating migraine and preparation method thereof - Google Patents
In-situ gel for treating migraine and preparation method thereof Download PDFInfo
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- CN102772459A CN102772459A CN2012102870823A CN201210287082A CN102772459A CN 102772459 A CN102772459 A CN 102772459A CN 2012102870823 A CN2012102870823 A CN 2012102870823A CN 201210287082 A CN201210287082 A CN 201210287082A CN 102772459 A CN102772459 A CN 102772459A
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Abstract
The invention relates to an in-situ gel for treating migraine and a preparation method thereof, relating to the field of medicinal preparation, and the invention particularly relates to nose in-situ gel prepared from radix angelicae and ligusticum wallichii and a preparation method thereof. According to the invention, 20g of in-situ gel comprises 0.1-0.5g of radix angelicae volatile oil, 0.1-0.5g of ligusticum wallichii volatile oil, 0.3-0.8g of dried radix angelicae and ligusticum wallichii extract, 0.1-2.6g of poloxamer, 3.2-4.2g of poloxamer 407 and the balance of water, the radix angelicae and ligusticum wallichii extract is prepared by extracting the radix angelicae and the ligusticum wallichii with same amount by 95% of ethanol, then loading macroporous adsorption resin columns, eluting by using pure water, 30% of ethanol and 80% of ethanol, collecting 80% of ethanol eluent, reducing pressure and distilling until no liquid evaporates. The in-site gel disclosed by the invention is delivered through the nasal cavity to be mainly used for treating the migraine, has the advantages of high curative effect, convenience in drug delivery, no invasion, anodynia and the like, and is simple and convenient in preparation process, and suitable for industrial production.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, the nose that is specifically related to process with the Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract is with temperature sensitive type in-situ gel agent and preparation method thereof.
Background technology
The prescription that cures mainly wind syndrome of head (migraine) that root of Dahurian angelica rhizome of chuanxiong looses and recorded in classical Chinese medicine " Prescriptions for Universal Relief " (bright) volume 46 is grouped into by the Radix Angelicae Dahuricae (Angelica Duhurica) and Rhizoma Chuanxiong (Liguisticum Chuanxiong) medicine equity.Its determined curative effect, prescription are simple, and tcm clinical practice is applied to migrainous prevention and treatment with this side for broad-based.Rhizoma Chuanxiong suffering temperature in the side, gas medicine in the blood, the special promoting flow of QI and blood of merit, wind-expelling pain-stopping, the hot temperature of the Radix Angelicae Dahuricae, aroma is dense, kind dispeiling pathogenic wind and removing dampness, understand things pain-stopping, the two phase 5, wind-expelling pain-stopping, the merit of promoting blood circulation to remove obstruction in the collateral should be cited.The main chemical compositions of Rhizoma Chuanxiong is a phthalide-type, like Ligustilide, cnidium lactone, and alkaloids such as ligustrazine, organic acid such as ferulic acid, volatile oil.Angelica dahurica coumarin effective site is its active substance basis, analgesic, has the effect of antipyretic-antalgic, antiinflammatory and blood vessel dilating, is index property composition with imperatorin and isoimperatorin.Yet; At present the root of Dahurian angelica rhizome of chuanxiong mode of taking of loosing still is the form of extract oral decoction or the direct nasal-cavity administration of former powder, has that onset is slow, effective ingredient is difficult to through shortcomings such as blood brain barrier, therefore is necessary to combine the thought of the modernization of Chinese medicine; Develop new dosage form and route of administration, to improve its curative effect.
Summary of the invention
The objective of the invention is to develop a kind of nasal-cavity administration treatment rapid-action, eutherapeutic in-situ gel of migraine and its preparation method is provided.
For reaching the object of the invention, the technical scheme of employing is the situ-gel of being processed by following raw material: in the 20g in-situ gel by
Radix Angelicae Dahuricae volatile oil 0.1 ~ 0.5g
Rhizoma Chuanxiong volatile oil 0.1 ~ 0.5g
The Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract are in dry product 0.3 ~ 0.8g
Poloxamer 188 0.1 ~ 2.6g
Poloxamer 407 3.2 ~ 4.2g
All the other are formed for water
The described Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract are that the Radix Angelicae Dahuricae and the Rhizoma Chuanxiong medical material of getting equivalent are used 95% alcohol reflux; Extracting solution filters, and the filtrate decompression distillation is concentrated into the half the of crude drug weight, macroporous adsorptive resins absorption on the solution behind 10 times of the dilute with waters; Carry out eluting with pure water, 30% ethanol, 80% ethanol successively again; Collect 80% ethanol elution, distilling under reduced pressure to no liquid steams, and is the extract of the Radix Angelicae Dahuricae and Rhizoma Chuanxiong.
Another technical problem to be solved by this invention provides the method for preparing of above-mentioned nasal in situ gel.
The preparation of nasal in situ gel comprises the following steps:
The preparation of A, the Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract
Get the Radix Angelicae Dahuricae and Rhizoma Chuanxiong medical material mixing that equivalent has been pulverized, add 95% alcohol reflux 1 ~ 2 hour of 6 ~ 10 times of medical material weight at every turn, extract 2 times; Extracting solution filters, and merges filtrating twice, and distilling under reduced pressure is concentrated into the half the of crude drug weight; Macroporous adsorptive resins absorption is carried out eluting with pure water, 30% ethanol, 80% ethanol more successively on the solution behind 10 times of the dilute with waters, collects 80% ethanol elution; Decompression and solvent recovery to no liquid steams; The gained concentrate is the Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract, measures the water content in the extract, calculates the dry product weight of the Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract;
The preparation of B, in-situ gel
Press in the gel of 20g by Radix Angelicae Dahuricae volatile oil 0.1 ~ 0.5g; Rhizoma Chuanxiong volatile oil 0.1 ~ 0.5g; The Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract be in dry product 0.3 ~ 0.8g, poloxamer 188 (being called for short P188) 0.1 ~ 2.6g, poloxamer 407 (being called for short P407) 3.2 ~ 4.2g; All the other are got the raw materials ready for the proportion of composing of water, are being lower than 20 after taking by weighing poloxamer 188 and the abundant swelling of poloxamer 407 waters
oContinuous stirring adds Radix Angelicae Dahuricae volatile oil, Rhizoma Chuanxiong volatile oil and Radix Angelicae Dahuricae Rhizoma Chuanxiong extract down in the C environment, and the abundant mixing of water that adds remainder again gets final product embedding in the collunarium bottle, and the back is in 20
oPreserve below the C.This in-situ gel is in nasal cavity temperature (33 ~ 35
oC) can change gel into by solution.
Radix Angelicae Dahuricae volatile oil and Rhizoma Chuanxiong volatile oil can adopt commercially available, also can adopt conventional steam distillation or supercritical carbon dioxide extraction method respectively from the Radix Angelicae Dahuricae, extract in the Rhizoma Chuanxiong medical material.
Nasal drug delivery system (Nasal Drug Delivery System; NDDS) be the preparation of bringing into play the Drug therapy effect through Nasal Mucosa Absorption, can treat part or systemic disease, have Noninvasive, painless, avoid characteristics such as first pass effect; Because the special physiological structure of nasal cavity; Medicine can also get around blood brain barrier through nasal cavity, directly gets into cerebral tissue, therefore can develop the treatment that is used for brain diseases.But there is the shortcoming of holdup time weak point, easy-clear in traditional nasal cavity administrated prepn (like nasal drop, nasal spray etc.); And situ-gel is liquid before administration; Because the variation meeting of environment (like temperature, pH etc.) becomes gel state by solution state, can improve the bioadhesive of preparation after the administration.Nasal in-situ gel has combined the double dominant of in-situ gel preparation and nasal-cavity administration approach, is a drug delivery system that is used to treat brain diseases that development potentiality is arranged very much.
Advantage of the present invention: 1, product of the present invention organically combines the advantage of situ-gel, the characteristics of nasal drug delivery system and the main disease to be treated that root of Dahurian angelica rhizome of chuanxiong looses, and diffusing this classic prescriptions of root of Dahurian angelica rhizome of chuanxiong is carried out skill upgrading, reaches the purpose that improves curative effect; 2, this product has convenient drug administration, Noninvasive, characteristics such as painless, can improve patient's compliance; 3, prescription is simple, preparation technology is easy, is fit to suitability for industrialized production.
Further set forth technical scheme of the present invention and progress through embodiment below.
The specific embodiment
Embodiment 1The preparation of the Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract
Get the Radix Angelicae Dahuricae, each 0.5kg of Rhizoma Chuanxiong of having pulverized, mixing adds 95% ethanol of 10 kg, reflux, extract, 2h, and extracting solution filters; Filtrate for later use, medicinal residues add 95% ethanol of 6 kg again, reflux, extract, 1h, and extracting solution filters; Merge filtrating twice, distilling under reduced pressure is concentrated into 0.5kg, and to 5kg, last macroporous adsorptive resins adsorbs with distilled water diluting; Water, 30% ethanol and 80% ethanol carry out eluting successively again, collect 80% ethanol elution, and decompression and solvent recovery to no liquid steams, and get the Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract 5.7g; Water content 1.0% is converted into dry product 5.6g, records imperatorin content 0.52% with HPLC, ferulaic acid content 2.35%.
Embodiment 2The preparation of the Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract
Get the Radix Angelicae Dahuricae, each 0.5kg of Rhizoma Chuanxiong of having pulverized, mixing adds 95% ethanol of 8 kg, reflux, extract, 1.5h, and extracting solution filters; Filtrate for later use, medicinal residues add 95% ethanol of 8kg again, reflux, extract, 1.5h, and extracting solution filters; Merge filtrating twice, distilling under reduced pressure is concentrated into 0.5kg, and to 5kg, last macroporous adsorptive resins adsorbs with distilled water diluting; Water, 30% ethanol and 80% ethanol carry out eluting successively again, collect 80% ethanol elution, and decompression and solvent recovery to no liquid steams, and get the Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract 6.3g; Water content 0.9% is converted into dry product 6.2g, records imperatorin content 0.62% with HPLC, ferulaic acid content 2.14%.
Embodiment 3The preparation of the Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract
Get the Radix Angelicae Dahuricae, each 0.5kg of Rhizoma Chuanxiong of having pulverized, mixing adds 95% ethanol of 10 kg, reflux, extract, 1h, and extracting solution filters; Filtrate for later use, medicinal residues add 95% ethanol of 8kg again, reflux, extract, 1h, and extracting solution filters; Merge filtrating twice, distilling under reduced pressure is concentrated into 0.5kg, and to 5kg, last macroporous adsorptive resins adsorbs with distilled water diluting; Water, 30% ethanol and 80% ethanol carry out eluting successively again, collect 80% ethanol elution, and decompression and solvent recovery to no liquid steams, and get the Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract 5.3g; Water content 1.9% is converted into dry product 5.2g, records imperatorin content 0.57% with HPLC, ferulaic acid content 2.28%.
Embodiment 4The preparation of in-situ gel (every 20g contains P188 0.1g, P407 3.2g)
Take by weighing poloxamer 407 16g, poloxamer 188 0.5g, add about 50g water, be lower than 20
oBe stirred to poloxamer in the C environment and dissolve fully, 20
oC is to make the abundant swelling of poloxamer more than the held 12h.Be lower than 20
oConstantly stir in the C environment and add Radix Angelicae Dahuricae volatile oil and each 0.5g of Rhizoma Chuanxiong volatile oil (obtaining) down with the vapor distillation extraction; The Radix Angelicae Dahuricae Rhizoma Chuanxiong extract 1.5g (being equivalent to dry product 1.49g) that adds embodiment 2; Restock water ad pond om is 100g, and fully mixing promptly obtains in-situ gel 100g.Be lower than 20
oProp up embedding in the collunarium bottle, by 20g/ in the C environment in 20
oPreserve below the C.
Embodiment 5The preparation of in-situ gel (every 20g contains P188 0.1g, P407 3.4g)
Take by weighing poloxamer 407 17g, poloxamer 188 0.5g, add about 50g water, be lower than 20
oBe stirred to poloxamer in the C environment and dissolve fully, 20
oC is to make the abundant swelling of poloxamer more than the held 12h.Be lower than 20
oConstantly stir in the C environment and add Radix Angelicae Dahuricae volatile oil and each 0.5g of Rhizoma Chuanxiong volatile oil (obtaining) down with the vapor distillation extraction; The Radix Angelicae Dahuricae Rhizoma Chuanxiong extract 2.0g (being equivalent to dry product 1.98g) that adds embodiment 2; Restock water ad pond om is 100g, and fully mixing promptly obtains in-situ gel 100g.Be lower than 20
oProp up embedding in the collunarium bottle, by 20g/ in the C environment in 20
oPreserve below the C.
Embodiment 6The preparation of in-situ gel (every 20g contains P188 0.2g, P407 3.6g)
Take by weighing poloxamer 407 18g, poloxamer 188 1g, add about 50g water, be lower than 20
oBe stirred to poloxamer in the C environment and dissolve fully, 20
oC is to make the abundant swelling of poloxamer more than the held 12h.Be lower than 20
oConstantly stir in the C environment and add Radix Angelicae Dahuricae volatile oil and each 1g of Rhizoma Chuanxiong volatile oil (obtaining) down with the vapor distillation extraction; The Radix Angelicae Dahuricae Rhizoma Chuanxiong extract 2.5g (being equivalent to dry product 2.48g) that adds embodiment 2; Restock water ad pond om is 100g, and fully mixing promptly obtains in-situ gel 100g.Be lower than 20
oProp up embedding in the collunarium bottle, by 20g/ in the C environment in 20
oPreserve below the C.
Embodiment 7The preparation of in-situ gel (every 20g contains P188 1.2g, P407 3.8g)
Take by weighing poloxamer 407 19g, poloxamer 188 6g, add about 50g water, be lower than 20
oBe stirred to poloxamer in the C environment and dissolve fully, 20
oC is to make the abundant swelling of poloxamer more than the held 12h.Be lower than 20
oConstantly stir in the C environment and add Radix Angelicae Dahuricae volatile oil and each 1.5g of Rhizoma Chuanxiong volatile oil (obtaining) down with the vapor distillation extraction; The Radix Angelicae Dahuricae Rhizoma Chuanxiong extract 3g (being equivalent to dry product 2.97g) that adds embodiment 2; Restock water ad pond om is 100g, and fully mixing promptly obtains in-situ gel 100g.Be lower than 20
oProp up embedding in the collunarium bottle, by 20g/ in the C environment in 20
oPreserve below the C.
Embodiment 8The preparation of in-situ gel (every 20g contains P188 1.4g, P407 4.0g)
Take by weighing poloxamer 407 20g, poloxamer 188 7g, add about 50g water, be lower than 20
oBe stirred to poloxamer in the C environment and dissolve fully, 20
oC is to make the abundant swelling of poloxamer more than the held 12h.Be lower than 20
oConstantly stir in the C environment and add Radix Angelicae Dahuricae volatile oil and each 2g of Rhizoma Chuanxiong volatile oil (obtaining) down with the vapor distillation extraction; The Radix Angelicae Dahuricae Rhizoma Chuanxiong extract 3.5g (being equivalent to dry product 3.47g) that adds embodiment 2; Restock water ad pond om is 100g, and fully mixing promptly obtains in-situ gel 100g.Be lower than 20
oProp up embedding in the collunarium bottle, by 20g/ in the C environment in 20
oPreserve below the C.
Embodiment 9The preparation of in-situ gel (every 20g contains P188 2.6g, P407 4.2g)
Take by weighing poloxamer 407 21g, poloxamer 188 13g, add about 50g water, be lower than 20
oBe stirred to poloxamer in the C environment and dissolve fully, 20
oC makes the abundant swelling of poloxamer to spend the night more than the held 12h.Be lower than 20
oConstantly stir in the C environment and add Radix Angelicae Dahuricae volatile oil and each 2.5g of Rhizoma Chuanxiong volatile oil (obtaining) down with the vapor distillation extraction; The Radix Angelicae Dahuricae Rhizoma Chuanxiong extract 4g (being equivalent to dry product 3.96g) that adds embodiment 2; Restock water ad pond om is 100g, and fully mixing promptly obtains in-situ gel 100g.Be lower than 20
oProp up embedding in the collunarium bottle, by 20g/ in the C environment in 20
oPreserve below the C.
Use below
Test Example is explained of the present inventionThe beneficial effect of in-situ gel
Test Example 1In-situ gel extracorporeal releasing test of the present invention
Test method: adopt the Franz diffusion cell, dialyzer is fixed between supply pool and the reception tank.It in the supply pool product of diffusing former powder of 0.5g root of Dahurian angelica rhizome of chuanxiong (Radix Angelicae Dahuricae, Rhizoma Chuanxiong medicinal powder are pressed mass ratio 1:1 and mixed) or 0.1g in-situ gel embodiment 9 of the present invention; Receiving liquid is Ringer ' s liquid-PEG400 (80:20) 7mL; In 15min, 30min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h and 24h sampling, and the reception liquid of additional respective volume.Institute's sample thief is with the filtering with microporous membrane of 0.22 μ m, receives imperatorin and content of ferulic acid in the liquid with high effective liquid chromatography for measuring, calculate each time point the cumulative release degree (
M t /
M) (table 1), to Log (
M t /
M)-Log
tPress equation Log (
M t /
M)=Log
k+
nLog
tCarry out linear fit, calculate release rate constant
kAnd empirical index number
n(table 2).
Result of the test:
Table 1 imperatorin, each time point cumulative release degree (%) of ferulic acid
Table 2 imperatorin, ferulic acid extracorporeal releasing test result
| Dosage form | Index components | n | k | R 2 |
| The root of Dahurian angelica rhizome of chuanxiong former powder that looses | Imperatorin | 0.950 | 0.289 | 0.9923 |
| In-situ gel of the present invention | Imperatorin | 0.917 | 8.260 | 0.9796 |
| The root of Dahurian angelica rhizome of chuanxiong former powder that looses | Ferulic acid | 1.114 | 0.828 | 0.9947 |
| In-situ gel of the present invention | Ferulic acid | 0.467 | 36.983 | 0.8728 |
*
nBe empirical index number,
kBe release rate constant,
R 2Be the goodness of fit
Conclusion: imperatorin and ferulic acid release rate constant are all apparently higher than the crude drug powder in the diffusing situ-gel of root of Dahurian angelica rhizome of chuanxiong, i.e. release is significantly faster than the diffusing crude drug powder of root of Dahurian angelica rhizome of chuanxiong.
Test Example 2The outer nasal mucosa permeability test of situ-gel
Test method: the rabbit nasal mucosa exsomatizes, and (whether the rabbit auricular vein is injected excessive urethane and is put to death, and takes off the nasal cavity front portion, carefully peel off the nasal mucosa of both sides and observe complete along nasal septum through experiment; Unabroken nasal mucosa is immersed in refrigerated Ringer ' the s liquid immediately; Subsequent use), adopt improvement Franz diffusion cell, the rabbit nasal mucosa is fixed between supply pool and the reception tank; The nasal cavity side is to supply pool, and effectively infiltrating area is 0.138cm
2It in the supply pool product of diffusing former powder of 0.25g root of Dahurian angelica rhizome of chuanxiong (Radix Angelicae Dahuricae, Rhizoma Chuanxiong medicinal powder are pressed mass ratio 1:1 and mixed) or 0.05g in-situ gel embodiment 9 of the present invention; Receiving liquid is Ringer ' s liquid-PEG400 (80:20) 4mL; In 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h and 24h sampling, and the reception liquid of additional respective volume.Institute's sample thief receives imperatorin and content of ferulic acid in the liquid with the filtering with microporous membrane of 0.22 μ m with high effective liquid chromatography for measuring, the calculating cumulative infiltration capacity (
Q), with
QTo the time
tMake linear regression, try to achieve slope d
Q/ d
t(table 3) calculates apparent infiltration coefficient by following formula
P App =(d
Q/ d
t) (1/
C 0 A),
C 0 (
w/
w) be supply pool initial drug concentration,
ABe the effective infiltrating area of nasal mucosa, the result sees table 4.
Experimental result:
Table 3 imperatorin, each time point accumulation transit dose (μ g) of ferulic acid
Table 4 imperatorin, the external nasal mucosa permeability test of ferulic acid result
* loose former powder relatively with root of Dahurian angelica rhizome of chuanxiong
P＜0.05
Conclusion: imperatorin and ferulic acid accumulation infiltration capacity change better linear in time, and the process that promptly sees through nasal mucosa is the zero level process, and the infiltration rate of situ-gel explains that greater than the diffusing former powder of the root of Dahurian angelica rhizome of chuanxiong situ-gel has the short effect of oozing.
Test Example 3Pharmacodynamic experiment
The level and the migrainous outbreak of neurotransmitter (like 5-HT) have stronger getting in touch in the brain, and the subcutaneous injection nitroglycerin can make neurotransmitter content declines such as the interior 5-HT of brain, thereby brings out migraine.
Laboratory animal: Wistar rat (180 ~ 220g, male or female)
The Nerve in Migraine Model modeling method: Wistar rat skin lower injection nitroglycerin 10mg/kg head occurs scratching one's head, gets rid of behind the injection nitroglycerin, climbs autonomic activities frequencies increases such as cage, tail biting, back and forth movement.
With the normal saline is blank, and the positive contrast medicine of maleic acid sumatriptan sheet (maleic acid sumatriptan sheet is ground, and it is subsequent use to add the water mixing) carries out pharmacodynamic experiment.
Experiment is divided into groups: (A) blank group: not administration, subcutaneous injection normal saline; (B) model control group: not administration, subcutaneous injection nitroglycerin (10mg/kg); (C) positive controls: maleic acid Shu Mapu (commercially available maleic acid sumatriptan sheet is scattered in the distilled water) gastric infusion group; (D) the diffusing suspension of root of Dahurian angelica rhizome of chuanxiong (extract of diffusing volatile oil of root of Dahurian angelica rhizome of chuanxiong and embodiment 2 is scattered in the distilled water) is irritated the stomach group; (E) the diffusing solution of root of Dahurian angelica rhizome of chuanxiong (extract of diffusing volatile oil of root of Dahurian angelica rhizome of chuanxiong and embodiment 2 is dissolved in 30% ethanol) nasal-cavity administration group; (F) in-situ gel nasal-cavity administration low concentration group of the present invention (embodiment 4 in-situ gels); (G) concentration group (embodiment 7 in-situ gels) in the in-situ gel nasal-cavity administration of the present invention; (H) in-situ gel nasal-cavity administration high concentration group of the present invention (embodiment 9 in-situ gels).
Experimental technique: get 48 of Wistar rats; Male and female half and half are divided into eight groups at random, 6 every group; Each group was pressed the preordering method successive administration 3 days; 0 ~ 10min after the modeling, 10 ~ 20min, 20 ~ 30min rat autonomic activities number of times (scratch one's head, get rid of head, climb the summation of cage, tail biting, back and forth movement number of times) are observed in subcutaneous injection nitroglycerin (10mg/kg) modeling (blank group injecting normal saline) after last day administration half an hour, and the result sees table 5.Behind modeling 4h, rat is put to death, separate cerebral tissue, weigh, the 0.1mol/L perchloric acid that adds pre-cooling (includes 0.3mM Na
2EDTA and 0.5mM sodium sulfite), ultrasonic homogenate, the centrifugal 10min of 12000rpm gets supernatant, with high effective liquid chromatography for measuring 5-HT concentration, calculates cerebral tissue 5-HT content, and the result sees table 6.
Experimental result
Diffusing different dosage form of table 5 root of Dahurian angelica rhizome of chuanxiong and route of administration are to the influence of Migraine Rats autonomic activities
* compare with model control group
P＜0.05
Diffusing different dosage form of table 6 root of Dahurian angelica rhizome of chuanxiong and route of administration are to the influence of Migraine Rats autonomic activities
| Group | Cerebral tissue 5-HT content (μ g/g) |
| The blank group | 1.68±0.59 * |
| Model control group | ?1.39±0.18 *** |
| Sumatriptan is irritated the stomach group | 1.52±0.23 |
| The root of Dahurian angelica rhizome of chuanxiong suspension oral gavage group of loosing | 1.46±0.20 *** |
| The root of Dahurian angelica rhizome of chuanxiong solution nasal-cavity administration group of loosing | 1.63±0.11 * |
| The in-situ gel nasal-cavity administration low concentration group | 1.66±0.13 * |
| Concentration group in the in-situ gel nasal-cavity administration | 1.72±0.19 ** |
| In-situ gel nasal-cavity administration high concentration group | 1.71±0.15 ** |
* compare with model control group
P＜0.05
* and model control group are relatively
P＜0.01
* * and blank group are relatively
P＜0.05
Conclusion: root of Dahurian angelica rhizome of chuanxiong looses the solution gastric infusion to the no influence of Migraine Rats autonomic activities; And loose solution nasal-cavity administration and in-situ gel nasal-cavity administration of sumatriptan gastric infusion, root of Dahurian angelica rhizome of chuanxiong all can significantly reduce the autonomic activities number of times of Migraine Rats in 30min, but in-situ gel nasal-cavity administration of the present invention is faster with respect to the above two onsets; To the aspect that influences of Migraine Rats cerebral tissue 5-HT content, behind administration 4h, the diffusing stomach group of irritating of root of Dahurian angelica rhizome of chuanxiong still is starkly lower than normal level, and 5-HT content recovers normal level in the Migraine Rats brain and diffusing solution nasal-cavity administration of root of Dahurian angelica rhizome of chuanxiong and in-situ gel nasal-cavity administration can make.Comprehensive above pharmacodynamic experiment result can explain, is prepared into nasal in-situ gel and can reaches fast, effectively treat migrainous purpose root of Dahurian angelica rhizome of chuanxiong is diffusing.
Claims (2)
1. one kind is used to treat migrainous in-situ gel, it is characterized in that: in the gel of 20g by
Radix Angelicae Dahuricae volatile oil 0.1 ~ 0.5g
Rhizoma Chuanxiong volatile oil 0.1 ~ 0.5g
The Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract are in dry product 0.3 ~ 0.8g
Poloxamer 188 0.1 ~ 2.6g
Poloxamer 407 3.2 ~ 4.2g
All the other are formed for water
The described Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract are that the Radix Angelicae Dahuricae and the Rhizoma Chuanxiong medical material of getting equivalent are used 95% alcohol reflux; Extracting solution filters, and the filtrate decompression distillation is concentrated into the half the of crude drug weight, macroporous adsorptive resins absorption on the solution behind 10 times of the dilute with waters; Carry out eluting with pure water, 30% ethanol, 80% ethanol successively again; Collect 80% ethanol elution, distilling under reduced pressure to no liquid steams, and is the extract of the Radix Angelicae Dahuricae and Rhizoma Chuanxiong.
2. method for preparing that is used to treat migrainous in-situ gel is characterized in that:
The preparation of A, the Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract
Get the Radix Angelicae Dahuricae and Rhizoma Chuanxiong medical material mixing that equivalent has been pulverized, add 95% alcohol reflux 1 ~ 2 hour of 6 ~ 10 times of medical material weight at every turn, extract 2 times; Extracting solution filters, and merges filtrating twice, and distilling under reduced pressure is concentrated into the half the of crude drug weight; Macroporous adsorptive resins absorption is carried out eluting with pure water, 30% ethanol, 80% ethanol more successively on the solution behind 10 times of the dilute with waters, collects 80% ethanol elution; Decompression and solvent recovery to no liquid steams; The gained concentrate is the Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract, measures the water content in the extract, calculates the dry product weight of the Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract;
The preparation of B, in-situ gel
Press in the gel of 20g Radix Angelicae Dahuricae volatile oil 0.1 ~ 0.5g again, Rhizoma Chuanxiong volatile oil 0.1 ~ 0.5g, the Radix Angelicae Dahuricae and Rhizoma Chuanxiong extract be in dry product 0.3 ~ 0.8g, poloxamer 188 0.1 ~ 2.6g, and poloxamer 407 3.2 ~ 4.2g, all the other are got the raw materials ready for the proportion of composing of water,
Be lower than 20 after taking by weighing the abundant swelling of poloxamer water
oConstantly stir in the C environment and add Radix Angelicae Dahuricae volatile oil, Rhizoma Chuanxiong volatile oil and Radix Angelicae Dahuricae Rhizoma Chuanxiong extract down, add the remaining abundant mixing of water again and get final product, embedding behind the collunarium bottle in 20
oPreserve below the C.
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Application publication date: 20121114 |