CN1695611A - Combination of ligusticum lactone, preparation method and application - Google Patents
Combination of ligusticum lactone, preparation method and application Download PDFInfo
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Abstract
A ligustilide composition is prepared from ligustilide and medicinal plant oil through proportionally mixing, stirring, wrapping by lecithin microspheres or softgel, and preparing emulsion or capsule. Its medical application is also disclosed.
Description
Technical field
The present invention relates to ligustilide composition and method of making the same and application, relate in particular to ligustilide Emulsion and soft capsule and preparation method thereof and application.
Background technology
The structure of ligustilide and physical property:
Structural formula:
Molecular formula and molecular weight: C
12H
14O
2190, degree of unsaturation is 6.
Chemical name: 3-butylidene-4,5-dihydro Phthalide
English chemical name: 3-butylidene-4,5-dihydrophthalide
English name: ligustilide
Character description: the grease of little yellow band fragrance, 168～169 ℃/6mmHg of boiling point.Dissolve in normal hexane, cyclohexane extraction, petroleum ether, ether, ethyl acetate, methanol etc.
The chemical constitution of ligustilide is a phthalide-type, be connected with active cyclobutenyl on 3, be the chemically unstable factor, under room temperature nature placement condition, multiple isomerization reactions such as dehydrogenation, oxidation, hydrolysis, degraded can take place, very easily be isomerizated into other cyclobutenyl furan lactone compounds, the long-time placement makes sample progressively be transformed into brown, heavy-gravity semisolid or solid by transparent clarification, flowable liquid, be oxidized to multiple complicated product and even last the disappearance, make troubles for preparation and preservation.Existing experiment shows that ligustilide is at room temperature preserved 15d purity and reduced to 41.97% by 99.48%, and GC the analysis showed that its catabolite is very complicated.
The unstability of ligustilide is not only bad for preservation, and limited the preparation and the application of ligustilide preparation.The store method of ligustilide has at present:
1. the people such as Li Guisheng of Shandong greenery pharmacy find after deliberation, reduce storage temperature, and ligustilide is basicly stable in the time of-20 ℃, referring to Li Guisheng, Ma Chengjun, Li Xiangyu etc., the stability study of ligustilide and the GCMS of isomerization product analyze [J], Chinese herbal medicine, 2000,31 (6): 405.The stability of ligustilide under condition of different temperatures sees Table 1.
Table 1 ligustilide examine stability result (content %)
| The placement condition | Detection time (d) | ||||
| ????0 | ????15 | ????30 | ????60 | ????90 | |
| The room temperature dark place | ????99.48 | ????41.97 | ????- | ????- | ????- |
| 4 ℃ of refrigerator cold-storages | ????99.48 | ????86.67 | ????- | ????- | ????- |
| -15 ℃ of refrigerator cold-storages | ????99.48 | ????99.39 | ????99.20 | ????99.24 | ????99.15 |
"-" expression has taken place obviously to reduce to detect because of the purity of ligustilide
2. Zhejiang University's girth newly waits the people to use PCM solvation effect model to carry out the quantum chemistry Theoretical Calculation, studied of the influence of dissolved dose of effect in conjunction with gas chromatogram to ligustilide stability, new referring to girth, Li Xinhua, the stability of ligustilide and the relation of solvation effect [J], Acta Pharmaceutica Sinica, 2001,36 (10): 793.Solvation effect studies show that to stability influence ligustilide stability in solvent strengthens greatly, through the gas chromatogram check, preserves 25d purity under the room temperature and reduce to 96.36% by 97.98% in chloroform, and the same terms drops to 91.24% in thiacyclohexane.The pure product ligustilide of bibliographical information is promptly have an appointment 58% isomerization of 15d at ambient temperature.Ligustilide is identical with isomerization approach in solvent in air, and just because the influence of solvation effect makes solute and solvent reaction system increase solvation energy, reaction activity increases, gross energy reduction and more stable.The result shows, extremely unstable in the air at normal temperatures as the ligustilide of estimating important conventional Chinese medicine quality such as Radix Angelicae Sinensis, Rhizoma Chuanxiong, but in solvent, preserve and to prevent its isomerized generation to a certain extent, the result of calculation proof is because the influence of solvation effect, make ligustilide more stable in solvent, polarity of solvent is also influential to the stability of ligustilide simultaneously.Suitable polar solvent as chloroform, can make ligustilide preserve at normal temperatures more stablely, provides the research basis for preparing and preserving ligustilide.
3. the people such as Li Hui of China Academy of TCM, in ligustilide, add suitable pharmaceutic adjuvant, and the changes of contents situation of index components is found before and after relatively adding: 3 kinds of stabilizing agents Stabilization all certain of experiment sieving to ligustilide, and wherein with the more remarkable effect of stabilizing agent B.The test data homogeneity of stabilizing agent C is relatively poor relatively, there is deviation on the same group between the data, possible cause is that ligustilide is therein due to the bad dispersibility, referring to Li Hui, Wang Yitao, the influence factor of ligustilide stability and stabilisation measure, Jiangxi College of Traditional Chinese Medicine journal 2003,15 (1): 56～57.The results are shown in Table 2.
Table 2 different stabilizers is to the influence of ligustilide content
| ?stabilizer | ????????????????????????time?of?detective | |||||
| ????0 | ????2 | ????4 | ????10 | ????15 | ????30 | |
| ?stabilizer?A ?stabilizer?B ?stabilizer?C | ????100 ????100 ????100 | ??99.30 ??99.84 ??101.37 | ??99.42 ??99.80 ??92.24 | ??96.95 ??99.77 ??95.44 | ???96.87 ???98.83 ???89.18 | ???90.61 ???96.15 ???85.53 |
Though have stabilizing agent B can stablize ligustilide, article does not provide concrete prescription, application is not seen in patent retrieval yet.
The method of above-mentioned protection ligustilide, except that 3 method the unknowns, all the other two methods are difficult to use in the industrialization preparation is produced, and 3 methods can't be used for reference owing to do not see prescription.
Because thereby the unstability of ligustilide causes preparing the difficulty of stable ligustilide preparation.At present, also temporary can not be for the ligustilide preparation of clinical practice.The inventor is devoted to seek a kind of stabilizing agent that improves ligustilide stability, and develops stable ligustilide preparation.
Summary of the invention
The object of the present invention is to provide a kind of stable ligustilide compositions, this ligustilide compositions is made up of ligustilide and medicinal plant oil at least, the effect of vegetable oil comes down to function of stabilizer, has improved the stability of ligustilide compositions greatly owing to the existence of vegetable oil.
Another object of the present invention is to provide above-mentioned ligustilide preparation of compositions method, this method is simple, reliable, is applicable to suitability for industrialized production.
A further object of the present invention is to provide the medical usage of above-mentioned ligustilide compositions.
Compositions of the present invention can further include water, polyhydric alcohol such as glycerol and PH regulator such as sodium hydroxide.
Medicinal plant oil of the present invention comprises that soybean oil, Oleum Arachidis hypogaeae semen, Oleum sesami, olive oil and Semen Allii Tuberosi wet goods can coexist with ligustilide, and can reach the vegetable oil of stablizing the ligustilide effect.The mass ratio of ligustilide and vegetable oil is 1: 1-1: 50.
The polyhydric alcohol in the compositions of the present invention such as the content of glycerol are 2-2.5%.
Ligustilide compositions of the present invention is preferably ligustilide Emulsion or soft capsule.
Ligustilide preparation of compositions method of the present invention mainly comprises the steps:
(1) disperse, dissolve ligustilide with vegetable oil: vegetable oil and ligustilide are pressed 1: 1-1: 50 mixed is even.
(2) bag covers with air-isolation and light: the vegetable oil that step (1) gained is contained ligustilide is wrapped in glue material ball or the capsule, or is wrapped in the formed microsphere of the liposome that comprises lecithin, with effective secluding air and light.
The mixed method of vegetable oil and ligustilide has two kinds in the step (1): a kind of is that vegetable oil directly mixes with ligustilide; Another kind is under lecithin participates in, and suitable vegetable oil and ligustilide, G ﹠ W form oil-in-water type lipid microsphere fat milk.
The various dosage forms of ligustilide compositions of the present invention can make according to conventional preparation method.The compositions that makes can be stablized and deposits three months to 3 years.
Compositions route of administration of the present invention comprises oral or drug administration by injection, and dosage is calculated as the 0.1mg-50mg/kg body weight with ligustilide.
Compositions of the present invention has the effect of treatment and prevention and microcirculation disturbance diseases associated.The result of pharmacological testing shows that this chemical compound has following pharmacological action:
1, shows good microcirculation improvement effect, 3.0,1.5, three dosage groups of 0.75mg/kg all can obviously improve blood flow state (P＜0.01), make blood fluidised form grain unhurried current be improved as line grain stream and grain stream influence to acute model of microcirculation obstacle due to the high molecular dextran is as follows: the influence to the velocity of blood flow fluidised form shows as:; The microangiography method shows all energy increasing blood flow speed of each dosage group, dwindles ear eye circulation time (P＜0.01).In addition, the microangiography method demonstrates also can obviously reduce microvascular leakage, reduces microvascular permeability (P＜0.01), and then stops the generation of edema.The scarlet degree of each dosage group blood of ligustilide is better than model group, and is similar to normal group.Therefore can be used for microcirculation disturbance treatment of diseases and prevention, comprise the treatment and the prevention of shock, diabetic complication, cardio-pulmonary function obstacle, disordered brain function and multiple organs failure etc.
2, ligustilide has the effect of remarkable reduction endotoxin shock mouse death rate, and its action intensity is better than dexamethasone.Its maximum characteristics are can effectively avoid because circulatory disturbance due to heavy dose of endotoxin show that mainly can to keep mouse temperature normal, and model group and Dexamethasone group animal heat descends sharply.Ligustilide group mortality rate is 30%, and the Dexamethasone group mortality rate is 60%, and the model group mortality rate is 80%.
3, ligustilide has the poverty-stricken syndromic effect of rats breathing due to the significant antagonism oleic acid, is embodied in remarkable reduction pulmonary edema, pulmonary congestion, improves the effect of respiratory function and decreased heart rate.
4, ligustilide has significant effect to antianginal, myocardial infarction.
The specific embodiment
Below will be described in detail, but be not intended to limit protection scope of the present invention by the ligustilide composition and method of making the same and the purposes of specific embodiment to desire protection of the present invention.
Embodiment 1:
The 295g ligustilide is dissolved in the 2680g soybean oil, utilizes conventional soft capsule preparation technology to be prepared into the soft capsule of loading amount for 250mg.After placing 1 year half, room temperature shows that content is basicly stable.The results are shown in Table 3.
Table 3 ligustilide examine stability result (content %)
| The placement condition | Detection time (d) | ||||
| ????0 | ????30 | ????180 | ????360 | ????540 | |
| The room temperature dark place | ????100 | ????99.35 | ????99.28 | ????98.45 | ????98.27 |
Embodiment 2:
In material-compound tank, add 5kg soybean oil (using the vacuum suction), be warming up to 80 ℃, add 0.6kg lecithin, stirred 5-8 minute, and added ligustilide 250g, the ON cycle pump after all scattering to lecithin, fluid in the material-compound tank and glycerin liquid are mixed in proportion, open high-speed stirred.Add caustic lye of soda (1moL/L), regulate PH6.0-7.Stop to stir, add and filter water for injection, stir, be colostric fluid, survey glycerol content, pH value (glycerol content 95%-105%, pH value: 6.0-7.0) to full dose 50000ml.The cooling colostric fluid starts the low pressure homogenizer to 55-60 ℃, allows colostric fluid in the homogenize of machine internal recycle, starts high pressure homogenizer, allows emulsion enter the homogenize of machine internal recycle, and homogenize is 10 times repeatedly.After preceding 9 homogenizes, all with emulsion by cools down to about 50-55 ℃, after the 10th homogenize, the emulsion temperature is cooled to 20 ± 3 ℃, pH value 6.0-7.0.Emulsion is filtered through the 5um filter through the low pressure homogenizer again, can packing get ligustilide lipid microsphere lipomul.After placing 3 months, room temperature shows that content is basicly stable.The results are shown in Table 4.
Table 4 ligustilide examine stability result (content %)
| The placement condition | Detection time (d) | ||||
| ????0 | ????15 | ????30 | ????60 | ????90 | |
| The room temperature dark place | ????100 | ????99.75 | ????99.56 | ????99.42 | ????99.18 |
Embodiment 3
The 60g ligustilide is dissolved in the 3000g soybean oil, utilizes technology to be prepared into loading amount and be the 250mg soft capsule.After placing 1 year half, room temperature shows that content is basicly stable.The results are shown in Table 5.
Table 5 ligustilide examine stability result (content %)
| The placement condition | Detection time (d) | ||||
| ????0 | ????30 | ????180 | ????360 | ????540 | |
| The room temperature dark place | ????100 | ????99.27 | ????99.09 | ????99.12 | ????98.77 |
Embodiment 4:
In material-compound tank, add 5kg soybean oil (using the vacuum suction), be warming up to 80 ℃, add 0.6kg lecithin, stirred 5-8 minute, and added ligustilide 150g, the ON cycle pump after all scattering to lecithin, fluid in the material-compound tank and glycerin liquid are mixed in proportion, open high-speed stirred.Add caustic lye of soda (1moL/L), regulate PH6.0-7.Stop to stir, add and filter water for injection, stir, be colostric fluid, survey glycerol content, pH value (glycerol content 95%-105%, pH value: 6.0-7.0) to full dose 50000ml.The cooling colostric fluid starts the low pressure homogenizer to 55-60 ℃, allows colostric fluid in the homogenize of machine internal recycle, starts high pressure homogenizer, allows emulsion enter the homogenize of machine internal recycle, and homogenize is 10 times repeatedly.After preceding 9 homogenizes, all with emulsion by cools down to about 50-55 ℃, after the 10th homogenize, the emulsion temperature is cooled to 20 ± 3 ℃, pH value 6.0-7.0.Emulsion is filtered through the 5um filter through the low pressure homogenizer again, can packing get ligustilide lipid microsphere Emulsion.After placing 3 months, room temperature shows that content is basicly stable.The results are shown in Table 6.
Table 6 ligustilide examine stability result (content %)
| The placement condition | Detection time (d) | ||||
| ????0 | ????15 | ????30 | ????60 | ????90 | |
| The room temperature dark place | ????100 | ????99.63 | ????99.48 | ????99.27 | ????99.31 |
Embodiment 5
The 100g ligustilide is dissolved in the 100g Oleum Arachidis hypogaeae semen, utilizes conventional soft capsule preparation technology to be prepared into the soft capsule of loading amount for 250mg.After placing 1 year half, room temperature shows that content is basicly stable.The results are shown in Table 3.
Table 7 ligustilide examine stability result (content %)
| The placement condition | Detection time (d) | ||||
| ????0 | ????30 | ????180 | ????360 | ????540 | |
| The room temperature dark place | ????100 | ????99.35 | ????99.17 | ????98.45 | ????97.38 |
Embodiment 6
The 10g ligustilide is dissolved in the 400g Oleum Brassicae campestris, utilizes conventional soft capsule preparation technology to be prepared into the soft capsule of loading amount for 250mg.After placing 1 year half, room temperature shows that content is basicly stable.The results are shown in Table 3.
Table 8 ligustilide examine stability result (content %)
| The placement condition | Detection time (d) | ||||
| ????0 | ????30 | ????180 | ????360 | ????540 | |
| The room temperature dark place | ????100 | ????98.24 | ????97.86 | ????97.25 | ????97.18 |
Embodiment 7
Ligustilide is to the protective effect of endotoxin shock mice.
Kunming mouse, 18 ± 2g, 100, be divided into 5 groups, be respectively dosage (BT-M) group, ligustilide heavy dose (BT-H) group and Dexamethasone group in model group, ligustilide low dose (BT-L) group, the ligustilide, wherein BT represents ligustilide, more than each expression mode be equally applicable to following each embodiment.
After each treated animal duplicated the mice endotoxin shock model, ligustilide was respectively organized gastric infusion, Dexamethasone group intraperitoneal injection, the survival rate of observing 24 hours mices, and animal ordinary circumstance and active state.The results are shown in Table 9.
Table 9 ligustilide is to the influence of endotoxin shock mouse death rate
| Group | Dosage (mg/kg) | Number of animals | Death toll |
| Model group BT-H BT-M BT-L dexamethasone | ????- ????10(ig) ????5(ig) ????2.5(ig) ????10(ip) | ????20 ????20 ????20 ????20 ????20 | ????17 ????6 ????10 ????14 ????12 |
As shown in Table 9, this model is successful.Model group and dexamethasone treated animal show as the whole body and feel cold, and color of the lip is blue, and each BT treated animal body temperature is normal, and no significance changes before color of the lip and the administration.Result of the test shows: ligustilide has the effect of remarkable reduction endotoxin shock mouse death rate.
Embodiment 8
Ligustilide is to the influence research of acute rabbit model of microcirculation obstacle due to the high molecular dextran
To be tried new zealand rabbit (body weight 2.0-2.5kg), be divided into 6 groups at random, 10 every group by body weight.Comprise 1. normal control group (NS); 2. model group (CONTROL); 3. BT-H organizes; 4. BT-M organizes; 5. BT-L organizes; 6. positive drug-NAODESHENG group (NDSH).
After setting up model, give the equal-volume normal saline with matched group and model group, other organizes gastric infusion, after 1 hour, and microcirculation situation after the observed and recorded administration.
1. the observation of blood fluidised form flow velocity
Measure according to field Sanguis Bovis seu Bubali flow velocity degree fractionation testing method.Its method is: according to the blood flow forms of motion, flow velocity is divided into seven grades: (1) linear flow (2) line grain stream (3) grain linear flow (4) grain stream (5) grain unhurried current (6) grain pendulum stream (7) is stagnated.
Result of the test is carried out the RIDIT analysis by computer utilization SAS software, and measurement result sees Table 10.
The fractionated influence of fluidised form flow velocity of acute rabbit microcirculation disturbance due to the table 10 couple DEXTRAN T500
| Group | Animal (only) | Dosage mg/kg | The classification of fluidised form flow velocity | Significance | |||
| Linear flow | Line grain stream | Grain stream | The grain unhurried current | ||||
| ?NS ?CONTROL ?BT-H ?BT-M ?BT-L ?NDSH | ?9 ?9 ?9 ?10 ?10 ?10 | ?- ?- ?3 ?1.5 ?0.75 ?327 | ?8 ?0 ?0 ?0 ?0 ?0 | ?1 ?0 ?4 ?3 ?3 ?2 | ?0 ?2 ?4 ?6 ?6 ?6 | ?0 ?7 ?1 ?1 ?1 ?2 | - ★★ ** ** ** ** |
Annotate: the administration group is compared with model group,
*Expression P＜0.01.
Model group is compared with matched group, and ★ ★ represents P＜0.01.
As shown in Table 10, model group is compared with normal group, and blood flow rate obviously slows down in the pia mater encephali blood capillary, becomes grain stream or grain unhurried current (P＜0.01) by normal linear flow, grain linear flow; Each dosage group of ligustilide and the administration of NAODESHENG group were compared with model group after 1 hour, all can obviously improve blood flow fluidised form (P＜0.01), and ligustilide is along with the increase of dosage, and drug effect has enhanced trend.
2. to the influence of erythrocyte aggregation
Reclassify method observed and recorded by the field cattle.Its method is divided into following three grades:
(1) erythrocyte is slightly assembled (2) erythrocyte moderate and is assembled the gathering of (3) erythrocyte severe.
Result of the test is carried out the RIDIT analysis by computer utilization SAS software, and measurement result sees Table 11.
The influence of acute rabbit microcirculation disturbance erythrocyte aggregation due to the table 11 couple DEXTRAN T500
| Group | Animal (only) | Dosage mg/kg | The erythrocyte aggregation classification | Significance | |||
| Do not have | Gently | In | Heavy | ||||
| ???NS ???CONTROL ???BT-H ???BT-M ???BT-L ???NDSH | ????9 ????9 ????9 ????10 ????10 ????10 | ????- ????- ????3.0 ????1.5 ????0.75 ????327 | ????9 ????0 ????0 ????0 ????0 ????0 | ????1 ????0 ????4 ????3 ????2 ????3 | ?0 ?8 ?5 ?6 ?7 ?6 | ??0 ??1 ??0 ??1 ??1 ??1 | - ★★ ** ** ** ** |
Annotate: compare with model group,
*Expression P＜0.01.
Model group is compared with matched group, and ★ ★ represents P＜0.01.
As shown in Table 11, the moderate gathering appears in erythrocyte in the model group blood capillary, occurs severe individually and assembles, and compares with the normal saline matched group, and erythrocyte aggregation is (P＜0.01) obviously; Each dosage group of ligustilide and the administration of NAODESHENG group all can improve erythrocyte aggregation (P＜0.01) after 1 hour.NAODESHENG PIAN is suitable to dosage group in the influence of erythrocyte aggregation and the ligustilide.
3. velocity of blood flow is measured: measure ear-eye circulation time with the microangiography method and represent
The influence of acute rabbit microcirculation disturbance velocity of blood flow due to the table 12 couple DEXTRAN T500 (x ± s)
| Group | Animal (only) | Dosage mg/kg | Ear eye circulation time (s) |
| ????NS ????CONTROL ????BT-H ????BT-M ????BTL ????NDSH | ????9 ????9 ????9 ????10 ????10 ????10 | ????- ????- ????3.0 ????1.5 ????0.75 ????327 | ??5.90±0.42 ??8.30±0.62★★ ????6.84+0.48 **??7.51±0.44 **??6.06±0.43 **??7.22±0.85 ** |
Annotate: compare with model group,
*Expression P＜0.01.
Model group is compared with matched group, and ★ ★ represents P＜0.01.
As shown in Table 12, with the matched group ratio, behind the quiet notes high molecular dextran of model group, ear eye circulation time obviously prolongs (P＜0.01); Each dosage group of ligustilide and the administration of NAODESHENG group all can obviously be shortened ear eye circulation time (P＜0.01) after 1 hour, and each group difference of ligustilide is not remarkable.
4. the observation of microvascular permeability change---show with the microangiography method
To observe the animal of ear eye circulation time, adopt the microcirculation scope to observe the variation of the inside and outside fluorescent material of blood capillary.With reference to the stage division of Pathophysiology teaching and research room of Shanghai Medical Univ, fluorescent material oozed out be divided into level Four: (1) is oozed out not obvious (-) (2) and is slightly oozed out (+) (3) moderate and ooze out (++) (4) severe and ooze out (+++)
Result of the test is carried out the RIDIT analysis by computer utilization SAS software, and measurement result sees Table 13.
The influence of acute rabbit microcirculation disturbance microvascular permeability due to the table 13 couple DEXTRAN T500 (x ± s)
| Group | Animal (only) | Dosage mg/kg | The permeability classification | Significance | |||
| ????- | ??+ | ??++ | ??+++ | ||||
| ???NS ???CONTROL ???BT-H ???BT-M ???BT-L ???NDSH | ????9 ????9 ????9 ????10 ????10 ????10 | ????- ????- ????3.0 ????1.5 ????0.75 ????327 | ????8 ????0 ????0 ????0 ????0 ????0 | ????1 ????0 ????3 ????3 ????2 ????2 | ????0 ????2 ????5 ????6 ????7 ????6 | ????0 ????7 ????1 ????1 ????1 ????2 | ????- ????★★ ????????** ????** ????** ????** |
Annotate: compare with model group,
*Expression P＜0.01.
Model group is compared with matched group, and ★ ★ represents P＜0.01.
As shown in Table 13, compare with matched group, behind the quiet notes high molecular dextran of model group, the outer fluorescent material showed increased (P＜0.01) of rabbit blood capillary; Each dosage group of ligustilide and the administration of NAODESHENG group all can obviously reduce the outer fluorescent material (P＜0.01) of pia mater encephali blood capillary after 1 hour, and each dosage group difference is not remarkable.
5. blood capillary morphologic observation
Observe by each treated animal being carried out microimaging, each dosage group of ligustilide all improves significantly to erythrocytic perfusion situation in erythrocyte aggregation, color, blood flow state, blood capillary periphery leakage and the blood capillary, and NAODESHENG PIAN does not have the improvement except that its color, and all the other indexs are basic identical with ligustilide.Simultaneously, the scarlet degree of each dosage group blood of ligustilide is better than model group, and is similar to normal group.
Embodiment 9
Ligustilide is to the poverty-stricken syndromic protective effect of rats breathing due to the oleic acid
With laboratory animal-SD male rat be divided at random normal control group, oleic acid cause injury group, oleic acid cause injury+BT-H, oleic acid cause injury+BT-M, oleic acid cause injury+BT-L, oleic acid cause injury+six groups of dexamethasone, the group of causing injury is slowly injected by 0.15ml/kg tail vein, and the normal control group is injected the equivalent normal saline.Give relative medicine after the injection immediately.Observe each treated animal and generally show, respiratory frequency, amplitude, are opened breast and are got lung after 6 hours in injection oleic acid, carry out pathological observation.
Result of the test
1. respiratory frequency and general state
Behind the animal injection oleic acid rapid breathing takes place gradually, die Blausucht.Ligustilide makes animal be in comparatively quietly state, and respiratory frequency is tending towards normally, and the die Blausucht phenomenon obviously alleviates.
2. pathological observation
Oleic acid damage group, the lung body expands, and the surface is kermesinus congestion and edema shape, sees the hemorrhage ecchymosis of the big lamellar of disperse, and tangent plane sees that the red foam-like liquid of volume overflows; Each dosage group lung volume of ligustilide is less, and apparent is bronzing, and congested degree is lighter, is dispersed in petechial hemorrhage and small pieces ecchymosis, and the rarely seen a small amount of pink foam sample liquid of tangent plane overflows.The blood stasis shape of dexamethasone improves not as the ligustilide group.
3. lung coefficient and lung wet/dry weight ratio
Oleic acid damage group lung coefficient and lung weight in wet base/dry weight ratio significantly increase; And ligustilide protection coefficient and lung weight in wet base/dry weight ratio all significantly reduce than oleic acid group, and the prompting pulmonary edema is alleviated.The results are shown in Table 12.
Table 12 ligustilide is to the influence of induced lung damage due to the oleic acid (x ± s)
| Group | Dosage (mg/kg) | Number of animals | The lung coefficient | Wet/dry weight ratio |
| Blank | ????- | ????10 | ????0.54±0.03 | ??5.40±0.49 |
| Model | ????- | ????10 | ????1.03±0.05☆☆ | ??7.10±0.65☆☆ |
| ????BT-H | ????10.0(ig) | ????10 | ????0.55±0.14★★ | ??3.28±0.94★★ |
| ????BT-M | ????5.0(ig) | ????10 | ????0.58±0.15★★ | ??4.18±1.49★★ |
| ????BT-L | ????2.5(ig) | ????10 | ????0.65±0.20★★ | ??4.93±1.61★★ |
| Dexamethasone | ????2.2(ip) | ????10 | ????0.62±0.10★★ | ??5.49±0.70★★ |
☆ ☆: compare with the blank group; ★ ★: compare with model group.
Claims (9)
1. the ligustilide compositions is characterized in that, said composition is made up of ligustilide and pharmaceutically useful vegetable oil, and the mass ratio of ligustilide and vegetable oil is 1: 1-1: 50.
2. compositions according to claim 1 is characterized in that, described compositions also comprises water, polyhydric alcohol and PH regulator, and wherein the weight content of polyhydric alcohol is 2-2.5%.
3. compositions according to claim 2 is characterized in that, wherein polyhydric alcohol is a glycerol, and the PH regulator is a sodium hydroxide solution.
4. compositions according to claim 1 and 2 is characterized in that described vegetable oil comprises soybean oil, Oleum Arachidis hypogaeae semen, Oleum sesami, olive oil and Oleum Brassicae campestris.
5. according to claim 1 or 2 or 3 described compositionss, it is characterized in that the existence form of described compositions is Emulsion or soft capsule.
6. compositions according to claim 4 is characterized in that, the existence form of described compositions is Emulsion or soft capsule.
7. a method for compositions for preparing claim 1-6 is characterized in that, this method may further comprise the steps:
(1) vegetable oil disperse, the dissolving ligustilide: with medicinal plant oil and ligustilide mix homogeneously by a certain percentage.
(2) bag covers air-isolation and light: the vegetable oil that will contain ligustilide is wrapped in glue material ball or the capsule, or comprises in the formed microsphere of liposome of lecithin, effectively secluding air and light.
8. method according to claim 7 is characterized in that, the vegetable oil in the step (1) and the mixed method of ligustilide have two kinds: a kind of is that the two directly mixes; Another kind is under lecithin participates in, and vegetable oil and ligustilide, G ﹠ W form oil-in-water type lipid microsphere fat milk.
9. the application of the compositions of claim 1-6 in the medicine of preparation treatment and prevention and microcirculation disturbance diseases associated.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410043159 CN1695611A (en) | 2004-05-12 | 2004-05-12 | Combination of ligusticum lactone, preparation method and application |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410043159 CN1695611A (en) | 2004-05-12 | 2004-05-12 | Combination of ligusticum lactone, preparation method and application |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100427078C (en) * | 2005-11-22 | 2008-10-22 | 深圳海王药业有限公司 | Decanoyl acetaldehyde compound and its medicinal composition |
| CN101829056A (en) * | 2010-05-26 | 2010-09-15 | 重庆工商大学 | Ligustilide fat emulsion and preparation method thereof |
-
2004
- 2004-05-12 CN CN 200410043159 patent/CN1695611A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100427078C (en) * | 2005-11-22 | 2008-10-22 | 深圳海王药业有限公司 | Decanoyl acetaldehyde compound and its medicinal composition |
| CN101829056A (en) * | 2010-05-26 | 2010-09-15 | 重庆工商大学 | Ligustilide fat emulsion and preparation method thereof |
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