CN1973847A - Nasal liquid medicine for treating headache and its prepn process - Google Patents
Nasal liquid medicine for treating headache and its prepn process Download PDFInfo
- Publication number
- CN1973847A CN1973847A CNA2006100225443A CN200610022544A CN1973847A CN 1973847 A CN1973847 A CN 1973847A CN A2006100225443 A CNA2006100225443 A CN A2006100225443A CN 200610022544 A CN200610022544 A CN 200610022544A CN 1973847 A CN1973847 A CN 1973847A
- Authority
- CN
- China
- Prior art keywords
- medicine
- nasal
- oil
- radix angelicae
- rhizoma chuanxiong
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention is one kind of nasal liquid medicine for treating headache and its preparation process. The medicine consists of volatile dahurian angelica oil and volatile Chuanxiong oil as the effective medicine components and pharmaceutically acceptable supplementary material. The medicine is prepared into emulsion form or gel form, such as nasal drop, nasal spray, aerosol, nasal inhalant, etc. The volatile oil as the effective component is preferably extracted through supercritical CO2 circular extraction and separation. The medicine for treating headache has high bioavailability and excellent effect.
Description
Technical field
The present invention relates to a kind of is the medicine of effective ingredient with the crude drug raw extract, more specifically says it is a kind of nasal liquid medicine by nasal delivery, and preparation method thereof.
Background technology
Migraine is a kind of commonly encountered diseases, frequently-occurring disease of Neurology Department, and sickness rate is the gesture of rising year by year.Though this disease is not fatal, have a strong impact on people's quality of life, and the normal work of influence.It is reported that only the economic loss should disease brought of the U.S. is annual about 55,000,000,000 dollars.Doctor trained in Western medicine does not still have unified understanding to pathogenesis of migraine at present, approves of it relevant with the nervous function disorder more.Chinese medicine belongs to migraine " wind syndrome of head " sick category, think that they are many because of due to ailment said due to cold or exposure attacks outward, and think that pneumatic, stagnation of phlegm, stasis are its main pathological factor, as migraine and general headache due to the wind and cold is the commonly encountered diseases of winter-spring season, pathogenesis is that ailment said due to cold or exposure is held the cold criminal's of going up head under the arm, the gas of clear sun is obstructed, and coagulation of QI-blood checks the network road and a headache.
The Radix Angelicae Dahuricae, Rhizoma Chuanxiong are the medicinal herbs most in use of treatment headache in the tcm clinical practice.The main effective ingredient of the Radix Angelicae Dahuricae is coumarin and volatile oil; The main effective ingredient of Rhizoma Chuanxiong is alkaloid, ferulic acid and volatile oil.A kind of oral medicine that the 1st patent medicine that records of the Sanitation Ministry medicine standard Chinese traditional patent formulation preparation " all beam balls " promptly is made up of the Radix Angelicae Dahuricae, Rhizoma Chuanxiong, the big honeyed pills of making for the powder and the refined honey 112.5g of every 100g Radix Angelicae Dahuricae, Rhizoma Chuanxiong, the heavy 9g of every ball, therapeutic dose is each oral 1 ball, 3 times on the one, it is obstructed to be used for the nasal obstruction that the heresy of wind and cold causes, migraine and general headache.Because ingredient only enters its therapeutical effect of blood brain barrier competence exertion, and the bioavailability of oral formulations is low, and onset is slow, and the medicinal ingredient that is absorbed into blood also often is difficult to see through blood brain barrier, has greatly influenced the drug effect performance of the Radix Angelicae Dahuricae and Rhizoma Chuanxiong.According to another reports such as Zhang Jilong (" the medical officer people " 1996 (5): 44),, can obtain good result with the scattered medicated powder snuffing treatment of Rhizoma Chuanxiong Radix Angelicae Dahuricae headache 120 examples.But it not only use inconvenience, and the drug level that can play a role is significantly low, and is unfavorable for the absorption of active ingredient with crude drug powder snuffing treatment, and the safety of medication is also relatively poor.
Summary of the invention
At above-mentioned situation, the present invention will provide a kind of nasal liquid medicine that is used for the treatment of headache, make it when being used for the headache treatment, can have better bioavailability and more superior drug action, rapid-action and reduced dosage significantly, greatly help saving consumption, and convenient patient uses to medical material.
The present invention treats the nasal liquid medicine of headache, be to be the active drug composition with Radix Angelicae Dahuricae volatile oil and Rhizoma Chuanxiong volatile oil, form jointly with the auxiliary adding ingredient of acceptable in the medicine, active drug component content ratio in the crude drug raw material is to contain effective ingredient total amount 200-2000g in every 100ml medicine, and wherein the part by weight of the Radix Angelicae Dahuricae and Rhizoma Chuanxiong is 1/0.2～2.As the Radix Angelicae Dahuricae volatile oil and the Rhizoma Chuanxiong volatile oil of active drug composition, can be extract, or adopt supercritical CO by the conventional vapor distillation of the crude drug raw material Radix Angelicae Dahuricae and Rhizoma Chuanxiong
2The corresponding volatile oil that circulation counter-current extraction, separation obtain.Because supercritical CO
2Abstraction technique can be preserved in good condition under cryogenic conditions, also optionally separate and enrichment volatile oil effective ingredient, the extraction efficiency height, and the active constituent content height, no solvent residue therefore can be preferably by supercritical CO
2The corresponding extractive of volatile oil that extraction obtains.
Become the solution-type pharmaceutical preparation of homogeneous phase for helping medicine, on the basis of above-mentioned composition, can also further select suitable solubilizing agent, to improve the solubility property of Radix Angelicae Dahuricae volatile oil and Rhizoma Chuanxiong volatile oil.As solubilizing agent poly yamanashi esters (can comprise polysorbas20, polysorbate40, polysorbate60, Tween 80 and polysorbate85 etc.), polyethylene glycols (can comprise PEG 400 and PEG 600 etc.), propylene glycol, TC (trade name Transcutol commonly used
P), mixture (the trade name Labrasol of glyceride and polyethylene glycol fatty acid
) etc.
Above-mentioned said nasal liquid medicine can be prepared into multiple dosage form for nasal-cavity administration, one of particularly preferred preparation wherein, be to comprise the O/W type Emulsion nasal liquid preparation of existing common breast, submicron emulsion, microemulsion or nano-emulsion at present, contain emulsifier component 0.2-10g in wherein every 100ml medicine, pharmaceutical grade oils composition 0-20g.Said emulsifier component, can be at surfactant-based, the sugar fatty acid esters of phospholipid at present commonly used, triglyceride, Tween 80, polyxyethylated esters, amine N-oxidation etc., as selecting for use a kind of or several in the compositions such as lecithin, soybean phospholipid, cholesterol, poloxamer (Poloxamer), HS15 (Polyethylene Glycol 12-hydroxy stearic acid ester, polyethylene glycol 660hydroxysterate), polyglycereol Palmic acid diol ester, Pluronic F68, glycerin mono-fatty acid ester.Said pharmaceutical grade oils composition is the vegetable oil composition, can in the vegetative grease composition that Gong the emulsion-type pharmaceutical preparation of existing report and/or use is at present used, select for use, as special recommendation is to use more soybean oil at present, and safflower oil, Oleum Gossypii semen, Semen Maydis oil, olive oil, Semen Sesami wet goods vegetative grease composition, can select mineral oil, synthetic ester oil or animal wet goods in addition for use, as hot certain herbaceous plants with big flowers acid glyceride, isopropyl myristate, liquid paraffin, Ethyl linoleate, silicone oil.
As required, can also add Off-Shoot-O triglyceride, oleic acid, sad, co-emulsifier such as certain herbaceous plants with big flowers is sour, lauric acid, linoleic acid, cholic acid as alcohols such as ethanol, n-butyl alcohol; As thickening agents such as arabic gum, tragacanth, cellulose derivatives; And conventional use ooze regulator as sodium chloride, glycerol, mountain plough alcohol, xylitol, glucose or the like; As antioxidants such as alpha-tocopherol, sodium pyrosulfite, sodium sulfite, sodium thiosulfate, ascorbic acid, cysteine; As pH regulator agent such as citric acid buffer salt, acetate buffer salt, phosphate-buffered salts; As antibacterial such as methaform, p-Hydroxybenzoate, sorbic acid, chlorobutanols; As penetration enhancer such as sodium laurylsulfate, chlolic acid derivatives, polyoxyethylene laurel ether, azone, Borneolum Syntheticums; But as in correctivess such as cinnamic aldehyde, vanillin, Oleum menthae, edible essence or the like other choosing subsidiary component one or more.Except that the said preparation form, be the gel-type medicine as alternative another kind of recommendation dosage form, can contain in every 100ml gel medicine just like carbomer, hypromellose, sodium carboxymethyl cellulose, chitosan, alginate isogel composition 0.2-4g.The advantage of gel medicine is the time of contact that can help prolong drug and nasal mucosa, improves bioavailability.Said medicine can be made as the form of multiple nasal cavity pharmaceutical preparatioies commonly used such as comprising nasal drop, nasal mist, aerosol or nasal cavity inhalant.
Because Radix Angelicae Dahuricae volatile oil and Rhizoma Chuanxiong volatile oil effective ingredient in the medicine of the present invention are clear and definite, active strong, and two volatile oil are the micromolecule liposoluble constituent, nasal mucosa infiltration rate and absorbance height, drug molecule is walked around blood brain barrier, directly enters the central nervous system and brings into play therapeutical effect.After particularly making O/W type Emulsion nasal liquid medicine preparation, the drug level height, thus when satisfying nasal-cavity administration dosage, reduce administration volume and administration number of times, increase the compliance of patient's medication.After making O/W type Emulsion, also help the stability that increases volatile oil component, and cover bad smell, improve permeability and minimizing the zest to organize of medicine, increase drug absorption, improve bioavailability mucosa.Therefore expelling wind and cold, promoting blood circulation to remove obstruction in the collateral effect and the effect performance of this nasal liquid medicine are given full play to, be specially adapted to as the caused nasal obstructions such as heresy of wind and cold obstructed, the headache of other reason such as migraine and general headache.
The preparation of said medicine of the present invention can be undertaken by subordinate's step:
1 '. the crude drug of the Radix Angelicae Dahuricae and Rhizoma Chuanxiong was pulverized 20 mesh sieves, with supercritical carbon dioxide cyclic countercurrent extraction 1～6 hour, extracting pressure 5～40Mpa, 30～70 ℃ of extraction temperature, per hour the circulate weight ratio of consumption of the inventory of the Radix Angelicae Dahuricae and Rhizoma Chuanxiong crude drug and carbon dioxide is 1: 4～20, the carbon dioxide that contains volatile oil component after the extraction is introduced the separator decompression separation by extractor, obtain the volatile oil of the Rhizoma Chuanxiong and the Radix Angelicae Dahuricae, and it is preheated to 50～80 ℃ as standby oil phase;
2 '. but emulsifying agent and other choosing subsidiary component are made dissolving with the aqueous dispersion stirring, form water and be heated to 50～80 ℃, but said other choosing subsidiary component comprises in acceptable co-emulsifier in the medicine, isoosmotic adjusting agent, antioxidant, thickening agent, pH regulator agent, antibacterial, penetration enhancer and the correctives one or more;
3 '. below 80 ℃, press the usual manner of Emulsion medication preparation, with above-mentioned oil phase and water full and uniform mix form colostrum after, again through high-pressure emulsification, can obtain uniform emulsion-type medicine.
Discover, above-mentioned 1 ' extraction process in, higher extracting pressure (as 30～40Mpa) and extraction temperature (as 60 ℃) condition under, the yield of the Radix Angelicae Dahuricae and/or Rhizoma Chuanxiong extract is higher, but the content of the ligustilide of effective ingredient is relatively low in the Rhizoma Chuanxiong; (as 10～20Mpa) and extraction temperature (as 40 ℃), though then the yield of the Radix Angelicae Dahuricae and/or Rhizoma Chuanxiong extract is lower, the content of corresponding effective ingredient ligustilide then can be higher and reduce extracting pressure.Therefore, in the practical application according to supercritical CO
2The performance of extraction equipment and concrete preparation demand can be selected the operating pressure and/or the temperature that suit during extraction.
In addition, when carrying out above-mentioned said supercritical carbon dioxide cyclic countercurrent extraction, the Radix Angelicae Dahuricae and Rhizoma Chuanxiong two crude drug raw materials can be extracted the back respectively and mix, or extraction simultaneously after will two raw materials mixing.
Below example by the specific embodiment again foregoing of the present invention is described in further detail.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following example.Do not breaking away under the above-mentioned technological thought situation of the present invention, various replacements or change according to ordinary skill knowledge and customary means are made include within the scope of the invention.
The specific embodiment
Embodiment 1
Radix Angelicae Dahuricae 160g and Rhizoma Chuanxiong 40g are packed in the conventional steam distillation device, adding distil water 8-12 doubly, with common oil water separator as the distillate gathering-device, water vapour distillation 4-6 hour, get the Radix Angelicae Dahuricae and Rhizoma Chuanxiong volatile oil, add 1.0ml Tween 80,10ml propylene glycol, 15ml Transcutol respectively
P and 10ml PEG 400, stirring and dissolving adds distilled water to an amount of, and is standby.Other gets sodium carboxymethyl cellulose 5g, adds an amount of distilled water placement and spends the night stirring and dissolving.Above-mentioned two kinds of solution are merged, and adding distil water stirs evenly to 100ml, is clarified, the solution of homogeneous, filters, and is sub-packed in the special-purpose collunarium bottle or in the spray bottle, promptly gets nasal drop or nasal spray.
Embodiment 2
The Radix Angelicae Dahuricae and Rhizoma Chuanxiong pulverize separately are crossed 20 mesh sieves, get Radix Angelicae Dahuricae 40kg and Rhizoma Chuanxiong 10kg, and mixing adopts supercritical fluid CO
2The circulation counter-current extraction with separate extracting pressure 10MPa, 35 ℃ of extraction temperature, extractant CO
2400 kilograms of consumptions/time, 4 hours extraction time, separator is resolved pressure 5Mpa, and 30 ℃ of resolution temperatures obtain the Radix Angelicae Dahuricae and the about 1.0kg of Rhizoma Chuanxiong volatile oil extract.Get extractive of volatile oil 200g, be preheated to 55 ℃ as oil phase, standby; Soybean phospholipid 12g adding distil water 500ml is disperseed, it is an amount of to add glycerol 24g, tragacanth 10g, ethyl hydroxybenzoate 1g and edible essence, stirs and makes dissolving, is heated to 55 ℃, and continue to stir, slowly add oil phase simultaneously, high speed homogenization made colostrum in 8 minutes, and colostrum is crossed high pressure dispersing emulsification machine circulation 6 times, adding distil water is to 1000ml under stirring at low speed, filtration, packing are put in the special-purpose collunarium bottle or in the spray bottle, promptly get nasal drop or spray.
Embodiment 3
Get Radix Angelicae Dahuricae coarse powder 33.3kg and Rhizoma Chuanxiong coarse powder 16.7kg, mix homogeneously adopts supercritical fluid CO
2The circulation counter-current extraction with separate extracting pressure 40MPa, 40 ℃ of extraction temperature, extractant CO
2500 kilograms of consumptions/time, 3 hours extraction time, separator is resolved pressure 10Mpa, and 35 ℃ of resolution temperatures obtain the Radix Angelicae Dahuricae and Rhizoma Chuanxiong volatile oil extract 1.6kg.Get extractive of volatile oil 200g, add Ovum Gallus domesticus Flavus lecithin 6g as oil phase; Get that sour 1g is ploughed on glycerol 25g, alpha-tocopherol 1g, mountain, carbomer 10g is dissolved in an amount of distilled water as water.Be heated to 55 ℃ respectively, mixing, in tissue mashing machine dispersion and emulsion 3-4 minute earlier, adding distil water was regulated pH value 6.0-7.0 to 1000ml again, through the emulsifying of high speed dispersing emulsification machine to oil droplet size less than 5 μ m.Packing is put in the special-purpose collunarium bottle, and every bottle of 10ml is described nasal drop.
Embodiment 4
Get Radix Angelicae Dahuricae coarse powder 25kg and Rhizoma Chuanxiong coarse powder 25kg, mix homogeneously adopts supercritical fluid CO
2The circulation counter-current extraction with separate extracting pressure 30MPa, 60 ℃ of extraction temperature, extractant CO
2600 kilograms of consumptions/time, 2 hours extraction time, separator is resolved pressure 8Mpa, and 50 ℃ of resolution temperatures obtain the Radix Angelicae Dahuricae and Rhizoma Chuanxiong volatile oil extract 1.8kg.Get extractive of volatile oil 150g, add soybean oil 50g, hot certain herbaceous plants with big flowers acid glyceride 10g, be preheated to 55 ℃ as oil phase, standby.Soybean phospholipid 12g adding distil water 500ml is disperseed, add glycerol 25g again, stir and make dissolving, be heated to 55 ℃, and continue to stir, slowly add oil phase simultaneously, high speed homogenization made colostrum in 6 minutes, and colostrum is crossed high pressure dispersing emulsification machine circulation 4 times, promptly got submicron emulsion.Under the stirring at low speed with the submicron emulsion adding distil water to 1000ml, filter, packing, put in the pressure vessel, add valve, sealing cap, be pressed into propellant, shake up, promptly get aerosol.
Embodiment 5
Get Radix Angelicae Dahuricae coarse powder 16.7kg and Rhizoma Chuanxiong coarse powder 33.3kg, mixing adopts supercritical fluid CO
2The circulation counter-current extraction with separate extracting pressure 15MPa, 35 ℃ of extraction temperature, extractant CO
2500 kilograms of consumptions/time, 2 hours extraction time, separator is resolved pressure 8Mpa, and 30 ℃ of resolution temperatures obtain the Radix Angelicae Dahuricae and Rhizoma Chuanxiong volatile oil extract 1.2kg.Get extractive of volatile oil 200g, be preheated to 70 ℃ as oil phase, standby; Soybean phospholipid 12g adding distil water 500ml is disperseed, it is an amount of to add glycerol 24g, tragacanth 10g, ethyl hydroxybenzoate 1g and edible essence, stirs and makes dissolving, is heated to 70 ℃, and continue to stir, slowly add oil phase simultaneously, high speed homogenization made colostrum in 8 minutes, and colostrum is crossed high pressure dispersing emulsification machine circulation 10 times, adding distil water is to 1000ml under stirring at low speed, filtration, packing are put in the special-purpose collunarium bottle or in the spray bottle, promptly get nasal drop or spray.
Embodiment 6
Get Radix Angelicae Dahuricae coarse powder 40kg and Rhizoma Chuanxiong coarse powder 10kg, mixing adopts supercritical fluid CO
2The circulation counter-current extraction with separate extracting pressure 8MPa, 40 ℃ of extraction temperature, extractant CO
2400 kilograms of consumptions/time, 3 hours extraction time, separator is resolved pressure 5Mpa, and 30 ℃ of resolution temperatures obtain the Radix Angelicae Dahuricae and the about 0.9kg of Rhizoma Chuanxiong volatile oil extract.Above-mentioned extractive of volatile oil is removed fatty acid (as Palmic acid, linoleic acid, hexadecanoic acid etc.) through molecular distillation, obtains quintessence oil 0.5kg.Get quintessence oil 200g, be preheated to 55 ℃ as oil phase, standby; Soybean phospholipid 12g adding distil water 500ml is disperseed, it is an amount of to add glycerol 24g, tragacanth 10g, ethyl hydroxybenzoate 1g and edible essence, stirs and makes dissolving, is heated to 55 ℃, and continue to stir, slowly add oil phase simultaneously, high speed homogenization made colostrum in 10 minutes, and colostrum is crossed high pressure dispersing emulsification machine circulation 8 times, adding distil water is to 1000ml under stirring at low speed, filtration, packing are put in the special-purpose collunarium bottle or in the spray bottle, promptly get nasal drop or spray.
Following pharmacodynamics test is used to prove beneficial effect of the present invention and positive effect.
1, the cilium toxicity test of medicine of the present invention
Adopt to exsomatize Bufo siccus maxillary model evaluation the foregoing description 1-6 medicine cilium toxicity (with reference to Jiang Xinguo etc., " Acta Pharmaceutica Sinica " 1995,30 (11): 848 method).The Bufo siccus maxillary mucomembranous cilium persistent movement time that it has been generally acknowledged that test group is more than 70% of physiology saline control group, can think that then the cilium toxicity of trial drug is less, belongs within clinical acceptable scope.Test shows that the drug administration of embodiment of the invention 1-6 is after 30 minutes, and the average relatively persistent movement time of Bufo siccus maxillary mucomembranous cilium shows that all more than 85% pharmaceutical preparation cilium toxicity of the present invention is little, and clinical drug safety the results are shown in Table 1.
Table 1 drug nasal drug-delivery preparation of the present invention nasal ciliary toxicity is estimated
| Pharmaceutical preparation of the present invention | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 | Embodiment 6 |
| The average relatively persistent movement time of Bufo siccus maxillary mucomembranous cilium (minute) | 86.5±4.9 | 91.1±5.3 | 90.8±4.5 | 93.0±6.2 | 92.5±5.7 | 88.1±5.0 |
2, medicine of the present invention and " all beam balls " controlled trial to experimental Nerve in Migraine Model rat behavior symptom influence
Use the emulsion-type liquid medicine as trial drug of the present invention with the nose of embodiment 2, carry out following test:
Get 50 of healthy Wistar rats, body weight is (300 ± 30) g, male and female half and half.Be divided into A, B, C, D at random, E organizes 5 groups, promptly normal control group (A), model group (B), Tai Ji TONGTIAN KOUFUYE are irritated stomach group (C), " all beam balls " fine powder is irritated stomach group (D) and trial drug collunarium group of the present invention (E), each treated animal is 10.According to Tassorelli C, the method for et al. (European J Pharmacol, 2003,464 (2-3): 159) improved, except that the normal control group, the equal subcutaneous injection Nitro-Bid of all the other each treated animals 9.50mg/kg duplicates experimental migraine animal model.Behind the about 3mim of administration, animal forelimb occurs and frequently scratches one's head, and dysphoria is climbed the cage increased frequency, gets rid of head, and the rubescent symptom that waits the head discomfort of ears is with its sign as the model copy success.Administration behind the 1mim appears in symptom: trial drug intranasal administration group of the present invention with micropipettor by 33.33 μ l (being equivalent to crude drug 0.33g)/kg intranasal administration; " all beam balls " fine powder gastric infusion group gives the Radix Angelicae Dahuricae and Rhizoma Chuanxiong crude drug powder 0.33g (suspension that is equivalent to 1.70ml)/kg; The Tai Ji TONGTIAN KOUFUYE is irritated the stomach group and is pressed the 1.70ml/kg gastric infusion; Normal control group and model group all give NS with micropipettor by the 33.33ul/kg collunarium.Result of the test is as follows:
(1) ear is red: the A group does not have the appearance of the red symptom of ear all the time, and learning by statistics to handle between other each group on the time of the red appearance of ear does not have significant difference.After the administration, learning result by statistics between each group on the red extinction time of ear shows: the D group does not have significance with B group comparing difference, and the C group all has significance (P＜0.001) with B group, E group with D group comparing difference with B group, E group, illustrate that emulsion-type liquid medicine intranasal administration of the present invention has curative effect preferably to migraine, and drug action does not appear in all beams ball fine powder gastric infusion of identical crude drug amount, the results are shown in Table 2.
(2) difficult to tackle: increasing of number of times difficult to tackle do not appear in the A group.B group and each treatment group rat in first time period (after being modeling about 3mim) begin to occur frequent action difficult to tackle, are not relatively having significant difference between each treatment group on the time that action difficult to tackle occurs.Learning result by statistics between each group on action remission time difficult to tackle after the administration shows: the D group does not have significance with B group comparing difference, and the C group all has significance (P＜0.001) with B group, E group with D group comparing difference with B group, E group, illustrate that emulsion-type liquid medicine intranasal administration of the present invention has curative effect preferably to migraine, and drug action does not appear in all beams ball fine powder gastric infusion of identical crude drug amount, the results are shown in Table 3.
(3) climb cage: rat occurs irritated after giving nitroglycerin, climbs the cage increased frequency, and it is similar with the result of action difficult to tackle to climb the result who climbs the time that cage reduces after time that the cage increased frequency occurs and the treatment, and both results are parallel, see Table 4.
The comparison of red appearing and subsiding time of table 2 rat ears
| Group | Dosage | The red time of occurrence of ear (min) | The red extinction time of ear (min) |
| A B C D E | 33.33ul/kg 33.33ul/kg 1.70ml/kg 1.70ml/kg 33.33ul/kg | 0.00 3.21±0.63 3.05±0.51 3.36±0.78 2.93±0.57 | 0.00 184.45±8.27 143.26±7.14▲ 179.73±9.38 87.32±7.65▲★ |
Annotate: compare with the B group: ▲ P＜0.001, compare with the D group: ★ P＜0.001.(down together)
The comparison of table 3 rat remission time difficult to tackle
| Group | Dosage | Time of occurrence (min) difficult to tackle | Go down the time (min) difficult to tackle |
| A B C D E | 33.33ul/kg 33.33ul/kg 1.70ml/kg 1.70ml/kg 33.33ul/kg | 0.00 3.35±0.60 3.12±0.82 3.27±0.69 3.04±0.73 | 0.00 187.24±8.01 138.75±7.68▲ 181.19±9.16 80.91±7.40▲★ |
Table 4 climb that cage occurs and administration after the comparison of remission time
| Group | Dosage | Climb cage time of occurrence (min) | Climb cage go down the time (min) |
| A B C D E | 33.33ul/kg 33.33ul/kg 1.70ml/kg 1.70ml/kg 33.33ul/kg | 0.00 3.94±0.73 3.65±0.69 3.80±0.81 3.48±0.87 | 0.00 190.50±8.01 141.06±7.68▲ 183.72±9.45 85.63±8.84▲★ |
Above-mentioned result of the test shows that fully nasal liquid medicine nasal ciliary toxicity of the present invention is little, and clinical drug safety migraine is had curative effect preferably, and all beams ball fine powder gastric infusion of identical crude drug amount does not have drug action.In general, nasal mist has better bioavailability and more superior drug action than nasal drop, and rapid-action and dosage greatly reduces, and has saved the consumption of medical material significantly, also convenient patient's use.Therefore, the present invention's nasal liquid medicine for the treatment of headache has gratifying DEVELOPMENT PROSPECT and value.
Claims (9)
1. treat the nasal liquid medicine of headache, it is characterized in that with Radix Angelicae Dahuricae volatile oil and Rhizoma Chuanxiong volatile oil be the active drug composition, form jointly with the auxiliary adding ingredient of acceptable in the medicine, active drug component content ratio in the crude drug raw material is to contain effective ingredient total amount 200-2000g in every 100ml medicine, and wherein the part by weight of the Radix Angelicae Dahuricae and Rhizoma Chuanxiong is 1/0.2～2.
2. the nasal liquid medicine of treatment headache as claimed in claim 1, it is characterized in that said medicine is the emulsion-type nasal formulations that comprises common breast, submicron emulsion, microemulsion or nano-emulsion, contain emulsifier component 0.2-10g in wherein every 100ml medicine, pharmaceutical grade oils composition 0-20g.
3. the nasal liquid medicine of treatment headache as claimed in claim 2 is characterized in that said pharmaceutical grade oils composition is the vegetable oil composition.
4. the nasal liquid medicine of treatment headache as claimed in claim 3 is characterized in that said vegetable oil composition is at least a in soybean oil, safflower oil, Oleum Gossypii semen, Semen Maydis oil, olive oil, the Oleum sesami.
5. the nasal liquid medicine of treatment headache as claimed in claim 1, it is characterized in that said medicine is the gel-type nasal formulations, contain gel component 0.2-4g in every 100ml medicine, said gel component is to comprise at least a in the composition of carbomer, cellulose derivative, chitosan and alginate.
6. the nasal liquid medicine of treatment headache as claimed in claim 1 is characterized in that said medicine is a kind of in nasal drop, nasal mist, aerosol or the nasal cavity inhalant.
7. the nasal liquid medicine of treatment headache as claimed in claim 1 is characterized in that Radix Angelicae Dahuricae volatile oil and the Rhizoma Chuanxiong volatile oil of said active drug composition for obtaining with the extraction of supercritical carbon dioxide circulation reflux type, separation.
8. prepare the method for the nasal liquid emulsion-type medicine of the described treatment headache of claim 1, step is as follows:
1 '. the crude drug of the Radix Angelicae Dahuricae and Rhizoma Chuanxiong was pulverized 20 mesh sieves, with supercritical carbon dioxide cyclic countercurrent extraction 1～6 hour, extracting pressure 5～40Mpa, 30～70 ℃ of extraction temperature, per hour the circulate weight ratio of consumption of the inventory of the Radix Angelicae Dahuricae and Rhizoma Chuanxiong crude drug and carbon dioxide is 1: 4～20, the carbon dioxide that contains volatile oil component after the extraction is introduced the separator decompression separation by extractor, obtain the volatile oil of the Rhizoma Chuanxiong and the Radix Angelicae Dahuricae, and it is preheated to 50～80 ℃ as standby oil phase;
2 '. but emulsifying agent and other choosing subsidiary component are made dissolving with the aqueous dispersion stirring, form water and be heated to 50～80 ℃, but said other choosing subsidiary component comprises in acceptable co-emulsifier in the medicine, isoosmotic adjusting agent, antioxidant, thickening agent, pH regulator agent, antibacterial, penetration enhancer and the correctives one or more;
3 '. below 80 ℃, press Emulsion medication preparation mode, mix above-mentioned oil phase and water are full and uniform, and behind high-pressure emulsification, obtain uniform emulsion-type medicine.
9. preparation method as claimed in claim 8, when it is characterized in that said supercritical carbon dioxide cyclic countercurrent extraction volatile oil, will the Radix Angelicae Dahuricae and Rhizoma Chuanxiong two crude drug raw materials mix after extraction simultaneously.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100225443A CN100536860C (en) | 2006-12-19 | 2006-12-19 | Nasal liquid medicine for treating headache and its preparation process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100225443A CN100536860C (en) | 2006-12-19 | 2006-12-19 | Nasal liquid medicine for treating headache and its preparation process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1973847A true CN1973847A (en) | 2007-06-06 |
| CN100536860C CN100536860C (en) | 2009-09-09 |
Family
ID=38124381
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100225443A Expired - Fee Related CN100536860C (en) | 2006-12-19 | 2006-12-19 | Nasal liquid medicine for treating headache and its preparation process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100536860C (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101406500A (en) * | 2008-12-04 | 2009-04-15 | 孙晓波 | Medicament for treating headache and migraine, and preparation method thereof |
| CN102772459A (en) * | 2012-08-14 | 2012-11-14 | 中山大学 | In-situ gel for treating migraine and preparation method thereof |
| CN104800446A (en) * | 2015-05-20 | 2015-07-29 | 宁夏医科大学 | Haheilili-extract nano-emulsion in-situ gel preparation and preparation method thereof |
| CN105640932A (en) * | 2016-01-07 | 2016-06-08 | 浙江医学高等专科学校 | Nasal spray and preparation method thereof |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106176949A (en) * | 2016-08-31 | 2016-12-07 | 天津中新药业研究中心 | A kind of compositions treating headache and preparation method thereof |
-
2006
- 2006-12-19 CN CNB2006100225443A patent/CN100536860C/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101406500A (en) * | 2008-12-04 | 2009-04-15 | 孙晓波 | Medicament for treating headache and migraine, and preparation method thereof |
| CN101406500B (en) * | 2008-12-04 | 2012-09-26 | 孙晓波 | Medicament for treating headache and migraine, and preparation method thereof |
| CN102772459A (en) * | 2012-08-14 | 2012-11-14 | 中山大学 | In-situ gel for treating migraine and preparation method thereof |
| CN104800446A (en) * | 2015-05-20 | 2015-07-29 | 宁夏医科大学 | Haheilili-extract nano-emulsion in-situ gel preparation and preparation method thereof |
| CN105640932A (en) * | 2016-01-07 | 2016-06-08 | 浙江医学高等专科学校 | Nasal spray and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100536860C (en) | 2009-09-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100536860C (en) | Nasal liquid medicine for treating headache and its preparation process | |
| CN1775261A (en) | Mingmu-Dihuang preparation and new preparing method | |
| CN1733081A (en) | Chinese medicine preparation for nourishing blood and tranquilizing mind and its preparation process | |
| CN1748748A (en) | Little leaf deervetch herb preparation for pregnant woman and new preparing method | |
| CN103830355B (en) | Oleum Nigellae nasal drop and preparation method thereof | |
| CN100404064C (en) | Medicine composition having functions of resisting virus and clearing heat and preparing method | |
| CN102091284B (en) | Xingnaojing oral emulsion for treating cerebral apoplexy and preparation method thereof | |
| CN101524448B (en) | Analgesic and anti-inflammatory Chinese medicinal composition as well as preparation method and application of preparation thereof | |
| CN101095700A (en) | Method for preparation of fermentation cordyceps active site and the application thereof in the aspect of respiratory disease | |
| CN1698717A (en) | Chinese medicinal compound fat emulsion injection and its preparation method | |
| CN102406890A (en) | Modified composition, preparation method and application thereof | |
| CN101897929B (en) | Improved composition as well as preparation method and application thereof | |
| CN1857492A (en) | Qingxie preparation and its preparing process | |
| CN1742926A (en) | Zuoci preparation for deaf and new preparing method thereof | |
| CN101653488A (en) | Application of Chinese medicinal composition in preparation of medicament for resisting myocardial stunning | |
| CN1833689A (en) | Asthma stop preparation and novel prepn. | |
| CN1253160C (en) | Medicine for treating fiver by nasal application and its preparing process | |
| KR102652851B1 (en) | Method for manufacturing Parenteral formulation using Cnidii Rhizoma | |
| CN113995782B (en) | Application of composition containing selfheal to preparation of medicine for treating thyroid nodules | |
| CN107028911A (en) | It is a kind of to treat Chinese medicine composition self-emulsifying soft capsule of hemorrhoid and preparation method thereof | |
| CN102178751B (en) | Brain clearing and pain relieving preparation | |
| US7288269B2 (en) | Asafetida extract as medicine for abstinence of drugs | |
| CN101530472A (en) | Preparation method and application of preparation for different extraction parts of biond magnolia flower | |
| CN1742824A (en) | Gynaecological Desheng preparation and new preparation method | |
| CN100348231C (en) | Medicine composition for resisting exogenous cold and high fever, and its preparing method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20090909 Termination date: 20111219 |