CN101244064A - Pharmaceutical combination for preventing and treating motion sickness and preparations thereof - Google Patents
Pharmaceutical combination for preventing and treating motion sickness and preparations thereof Download PDFInfo
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Abstract
The invention relates to a drug composition for the treatment of motion sickness, as well as the preparation, wherein the drug composition comprises caffeine and chlorpheniramine maleate; 50 to 500 mg caffeine and 2 to 20 mg chlorpheniramine maleate are contained in each preparation unit; the preferred mass ratio of caffeine to chlorpheniramine maleate in each composition is 50:2 and the preferred amount of each component is 200 mg caffeine and 8mg chlorpheniramine maleate. The drug composition has an advantage of effectively treating and preventing motion sickness without side effect of sleepiness or lassitude; besides, conventional adjuvant can be added in the drug composition to make drugs through any conventional method for motion sickness treatment; controlled release technologies can also be adopted to make controlled release preparations.
Description
Affiliated technical field
The present invention relates to a kind of pharmaceutical composition and preparation thereof that is used to prevent and treat motion sickness.
Background technology
Motion sickness is a kind of commonly encountered diseases, be because the vestibulum auris internae statoreceptor is subjected to the motion stimulation, and produce the autonomic nervous system dysfunction that excessive bio electricity causes, mostly occur when vehicles rotation of taking or turning, or startup, acceleration and deceleration brake, boats and ships rock, jolt, when elevator and aircraft lifting and landing.Everyone has a limit to intensity and the toleration of time that motion stimulates, and this limit causes dizzy threshold value exactly.Certain limit and in the time people can not produce untoward reaction, if stimulation has surpassed this limit and the motion sickness symptom will occur, tired sense or dizzy appears earlier usually, occur immediately yawning, sialorrhea and swallowing act increase, uncomfortable in chest, feel suffocated, symptom such as headache, take place subsequently to feel sick, vomiting; Part patient stomachache, blurred vision, frons severe pain, pale complexion, whole body cold sweat, pulse occur and crosses slow or overrun; Severe patient can have blood pressure drops, collapse.This dizzy, belong to one of peripheral vertigo, be more common in the person of having a delicate constitution, be many with the women especially.High humidity, high temperature, improper ventilation, physical weakness, do not have enough sleep, overtired, hungry or the satiety, psychentonia such as anxiety, depression and noise, unhappy abnormal smells from the patient such as pessimal stimulations such as smell of petrol, fishy smell, disease of inner ear etc. all can bring out or increase the weight of symptom.
At present, motion sickness agent thing side effect main on the market is many, side effect such as drowsiness weak, blurred vision and memory is impaired can occur with the user especially, but also have the drug withdrawal rebound phenomenon, brings inconvenience for tourism, life.
Summary of the invention
The purpose of this invention is to provide a kind of pharmaceutical composition and preparation thereof that is used for the treatment of motion sickness, the preferred mass proportioning of this pharmaceutical composition is: caffeine: chlorphenamine maleate=50: 2, each ingredients (preparation) unit content of caffeine is that 50～500mg, chlorphenamine maleate content are 2～20mg, and its preferred dose contains caffeine 200mg, chlorphenamine maleate 8mg for each ingredients (preparation) unit.
The medicine that pharmaceutical composition of the present invention is made has the effect of prevention and treatment motion sickness.Adopt the pharmaceutical composition that reaches of the present invention can treat the generation of motion sickness symptom and prevention motion sickness, and cause drowsiness taking Shi Buhui, the side effect of lassitude, this pharmaceutical composition can add conventional adjuvant, be prepared into the medicine of treatment motion sickness according to any conventional method, also can adopt slow controlled-release technology to be made into sustained-release preparation, adopt official method to measure its drug dissolution, the result shows that medicine continues to discharge, has slow-releasing and controlled-releasing action, make patient in a period of time, not need to take medicine once more and can not produce the cinetosis phenomenon, and do not have drowsiness, the side effect of lassitude.
The specific embodiment
The present invention is described further below in conjunction with embodiment.
Embodiment 1:
Get caffeine 200g, chlorphenamine maleate 8g.Earlier chlorphenamine maleate 8g is added starch 30g mixing, with the caffeine mixing, add micropowder silica gel 2g more again, mixing in 1000 capsules of packing into, promptly gets capsule.
Embodiment 2:
Get caffeine 200g, chlorphenamine maleate 8g adds starch 30g mixing again, adds micropowder silica gel 2g again, and mixing in 1000 capsules of packing into, promptly gets capsule.
Embodiment 3:
Get caffeine 200g, chlorphenamine maleate 8g.Earlier chlorphenamine maleate 8g is added starch 130g mixing, again with the caffeine mixing, wet granulation, particle drying adds micropowder silica gel 2g, and mixing is pressed into 1000, promptly gets tablet.
Embodiment 4:
Get caffeine 200g, chlorphenamine maleate 8g.With caffeine 200g, add starch 38 grams earlier, add micropowder silica gel 2g, mixing is in 1000 capsules of packing into.Again chlorphenamine maleate 8g is added starch 30g mixing, adds starch 200g mixing again, add micropowder silica gel 2g again, mixing, pack into 1000 of the capsules of the different colours of aforementioned dress caffeine in.Two kinds of capsules are respectively obeyed 1 respectively when taking.
Embodiment 5:
Get caffeine 200g, chlorphenamine maleate 8g.With caffeine 200g, add starch 38 grams earlier, wet granulation, particle drying adds micropowder silica gel 2g, and mixing is pressed into 1000, coating.Again chlorphenamine maleate 8g is added starch 30g mixing, add starch 200g mixing again, wet granulation, particle drying adds micropowder silica gel 2g, and mixing is pressed into 1000, the clothing layer of bag and aforementioned caffeine tablet different colours.Two kinds of sheets are respectively obeyed 1 respectively when taking.
Embodiment 6:
Get caffeine 200g, chlorphenamine maleate 8g.Earlier chlorphenamine maleate 8g is added dextrin 30g mixing, with the caffeine mixing, add micropowder silica gel 2g more again, mixing in 1000 capsules of packing into, promptly gets capsule.
Embodiment 7:
Get caffeine 200g, chlorphenamine maleate 8g.Earlier chlorphenamine maleate 8g is added dextrin 130g mixing, again with the caffeine mixing, wet granulation, particle drying adds micropowder silica gel 2g, and mixing is pressed into 1000, promptly gets tablet.
Embodiment 8:
Get caffeine 200g, chlorphenamine maleate 8g.With caffeine 200g, add dextrin 38 grams earlier, add micropowder silica gel 2g, mixing is in 1000 capsules of packing into.Again chlorphenamine maleate 8g is added dextrin 30g mixing, adds dextrin 200g mixing again, add micropowder silica gel 2g again, mixing, pack into 1000 of the capsules of the different colours of aforementioned dress caffeine in.Two kinds of capsule gradation are respectively obeyed 1 respectively when taking.
Embodiment 9:
Get caffeine 200g, chlorphenamine maleate 8g.With caffeine 200g, add dextrin 38 grams earlier, wet granulation, particle drying adds micropowder silica gel 2g, and mixing is pressed into 1000, coating.Again chlorphenamine maleate 8g is added dextrin 30g mixing, add dextrin 200g mixing again, wet granulation, particle drying adds micropowder silica gel 2g, and mixing is pressed into 1000, the clothing layer of bag and aforementioned caffeine tablet different colours.Two kinds of sheet gradation are respectively obeyed 1 respectively when taking.
Embodiment 10:
Get caffeine 200g, chlorphenamine maleate 8g.Get chlorphenamine maleate, add hydroxypropyl methylcellulose 80g, sucrose 40, take by weighing dextrin 110g again, mix homogeneously through pulverizing 60 mesh sieves, with 95% alcoholic solution is that binding agent is made soft material, crosses 20 mesh sieves and granulates drying, 20 mesh sieve granulate, dried granule adds 1% magnesium stearate, mixing, tabletting, every heavy 0.24g, coating promptly gets slow-release tablet, and the dissolution test shows that it slowly discharged in 24 hours.Getting caffeine 200g, add starch 38g, is that binding agent is made soft material with water, cross 20 mesh sieves and granulate drying, 20 mesh sieve granulate, dried granule adds 1% magnesium stearate, mixing, tabletting, every heavy 0.24g, earlier with the hydroxypropyl methylcellulose coating, sugar coating again, that is, the dissolution test shows that it releases 1 hour processus aboralis.Two kinds of sheet gradation are respectively obeyed 1 respectively when taking.
Embodiment 11:
Get caffeine 200g, chlorphenamine maleate 8g.Get chlorphenamine maleate, add hydroxypropyl methylcellulose 80g, sucrose 40, take by weighing dextrin 110g again, mix homogeneously through pulverizing 60 mesh sieves, with 95% alcoholic solution is that binding agent is made soft material, crosses 20 mesh sieves and granulates drying, 20 mesh sieve granulate, dried granule adds 1% magnesium stearate, mixing, tabletting, every heavy 0.12g, coating promptly gets slow-release tablet, and the dissolution test shows that it slowly discharged in 24 hours.Getting caffeine 200g, add starch 38g, is that binding agent is made soft material with water, cross 20 mesh sieves and granulate, and drying, 20 mesh sieve granulate, dried granule adds 1% magnesium stearate, mixing, tabletting, every heavy 0.12g, the dissolution test shows that it releases 1 hour processus aboralis.In each two same capsules of packing into of above-mentioned two kinds of tablets, promptly get and delay controlled release microplate capsule.
Embodiment 12:
Get caffeine 200g, chlorphenamine maleate 8g.Get chlorphenamine maleate, add hydroxypropyl methylcellulose 80g, sucrose 40, take by weighing dextrin 110g again through pulverizing 60 mesh sieves, mix homogeneously, fluid bed bag method is made microsphere, and the dissolution test shows that it slowly discharged in 24 hours.Getting caffeine 200g, add starch 38g, is that binding agent is made soft material with water, cross 20 mesh sieves and granulate, and drying, 20 mesh sieve granulate are made microsphere, and the dissolution test shows that it releases 1 hour processus aboralis.Above-mentioned two kinds of microsphere mixings are packed in the same capsule, promptly get and delay the control-release microsphere capsule.
Embodiment 13:
Get caffeine 200g, chlorphenamine maleate 8g.Get chlorphenamine maleate, add hydroxypropyl methylcellulose 80g, sucrose 40, take by weighing dextrin 110g again through pulverizing 60 mesh sieves, mix homogeneously, fluid bed bag method is made microsphere, and the dissolution test shows that it slowly discharged in 24 hours.Getting caffeine 200g, add starch 38g, is that binding agent is made soft material with water, cross 20 mesh sieves and granulate, and drying, 20 mesh sieve granulate are made microsphere, and the dissolution test shows that it releases 1 hour processus aboralis.Above-mentioned two kinds of microspheres are respectively charged in the different capsules, respectively take one respectively when taking.
Embodiment 14: alternation acceleration rotatory stimulation is caused the dizzy influence of rabbit
1. material
1.1 the laboratory animal new zealand white rabbit, body weight 2～2.5kg, male and female half and half are provided by No.1 Military Medical Univ.'s Experimental Animal Center.
1.2 medicine and reagent dimenhydrinate; Chlorphenamine maleate; Caffeine; Compositions: combine by 50: 2 weight ratios by caffeine and chlorphenamine maleate.
1.3 the program control single board computer of the attached TP-80 of the electronic swivel chair of instrument JKY-II type (Beijing IAM); RM26000 type eight road physiology monitors (Japanese photoelectricity company); TDS2000B oscillograph (Imtech).
2. method
Get 96 of new zealand white rabbits, be divided into 12 groups at random, it is the normal control group, model control group, the dimenhydrinate group, chlorphenamine maleate low dose group (being equivalent to adult's clinical equivalent dosage 2mg/ time), dosage group in the chlorphenamine maleate (being equivalent to adult's clinical equivalent dosage 8mg/ time), chlorphenamine maleate high dose group (being equivalent to adult's clinical equivalent dosage 20mg/ time), caffeine low dose group (being equivalent to adult's clinical equivalent dosage 50mg/ time), dosage group in the caffeine (being equivalent to adult's clinical equivalent dosage 200mg/ time), caffeine high dose group (being equivalent to adult's clinical equivalent dosage 500mg/ time), compositions low dose group (being equivalent to adult's clinical equivalent dosage 52mg/ time), dosage group in the compositions (being equivalent to adult's clinical equivalent dosage 208mg/ time), compositions high dose group (being equivalent to adult's clinical equivalent dosage 520mg/ time), 8 every group.Cause motion sickness dizzy to rabbit with rotatory stimulation, its concrete grammar is: rabbit is fixed on the electronic swivel chair, fixing rabbit head, make interior outer canthus line of its eyes and ground level be 30 ° of angles, make when moving with angular acceleration, horizontal semicircular canal is subjected to maximal stimulus, with two No. 5 rustless steel acupuncture needles insert in the rabbit left eye respectively and the last corner of the eyes to leave the 0.5cm place subcutaneous, depth of needle is that 0.5-1.0cm is as leading electrode.The nystagmus signal is imported physiograph through leading electrode, traces the nystagmus waveform by the oscillograph supervision and through pen.Rabbit is covered eye, leave standstill 15 minutes after, start electronic swivel chair, electronic swivel chair angular acceleration is 15 °/s
2, 8 seconds acceleration time, peak angular velocity is 120 °/s, and rolling nystagmus appears in rabbit, at the uniform velocity rotates 52 seconds, shuts down (stopping in 0.5 second), and the back nystagmus appears changeing in rabbit.By to rabbit electronystagmogram peak period slow phase velocity slope and the analysis of nystagmus persistent period, observe rabbit 30,60,90,150 minutes electronystagmogram indexs before medication and after the medication, judge that medicine is to dizzy possible curative effect.
3. result
By table 1,2 as seen, basic, normal, high dosage composition and middle and high dosage chlorphenamine maleate and dimenhydrinate can obviously suppress the slow phase velocity and the persistent period of rabbit nystagmus due to the alternation acceleration rotatory stimulation.Proof compositions, chlorphenamine maleate and dimenhydrinate have better curative effect to motion sickness dizzy.
Annotate: compare with model control group:
*P＜0.05;
*P＜0.01.
Table 2 is subjected to the reagent thing alternation acceleration rotatory stimulation to be caused the influence (n=8) of rabbit nystagmus persistent period
Annotate: compare with model control group:
*P＜0.05;
*P＜0.01.
Embodiment 15:
Alternation acceleration rotatory stimulation is caused the influence of rat vomiting
1. material
1.1 laboratory animal SD rat, male and female half and half, body weight 200～250g is provided by No.1 Military Medical Univ.'s Experimental Animal Center.
1.2 medicine and reagent dimenhydrinate; Chlorphenamine maleate; Caffeine; Compositions: combine by 50: 2 weight ratios by caffeine and chlorphenamine maleate; The Kaolin preparation: add water by Kaolin and arabic gum by 100: 1 weight ratios and be mixed and made into, shape is identical with feedstuff.
1.3 the program control single board computer of the attached TP-80 of the electronic swivel chair of instrument JKY-II type (Beijing IAM).
2. method
Get 120 of SD rats, be divided into 12 groups at random, it is the blank group, model control group, the dimenhydrinate group, chlorphenamine maleate low dose group (being equivalent to adult's clinical equivalent dosage 2mg/ time), dosage group in the chlorphenamine maleate (being equivalent to adult's clinical equivalent dosage 8mg/ time), chlorphenamine maleate high dose group (being equivalent to adult's clinical equivalent dosage 20mg/ time), caffeine low dose group (being equivalent to adult's clinical equivalent dosage 50mg/ time), dosage group in the caffeine (being equivalent to adult's clinical equivalent dosage 200mg/ time), caffeine high dose group (being equivalent to adult's clinical equivalent dosage 500mg/ time), compositions low dose group (being equivalent to adult's clinical equivalent dosage 52mg/ time), dosage group in the compositions (being equivalent to adult's clinical equivalent dosage 208mg/ time), compositions high dose group (being equivalent to adult's clinical equivalent dosage 520mg/ time), 10 every group.After the rat random packet, adaptability raised for 1 week in advance, allowed it freely ingest, to drink water, and Kaolin and feedstuff branch open in the crib that cage covers, and experimentize after 1 week.Rat is caused the motion sickness vomiting reaction with rotatory stimulation, and its concrete grammar is: rat is put into the lucite cage of rotary apparatus chainlessly, turn clockwise around trunnion axis, with 16 °/s
2Angular acceleration quickens, reach 120 °/s of maximal rate after, immediately with 48 °/s
2Angular acceleration slow down, stopping until rotation is 1 cycle, 10 seconds time, so repetitious stimulation is 1 hour.Give above-mentioned rotatory stimulation with after bringing out that rat is different and having a liking for the Kaolin behavior, observe respectively being subjected to the reagent thing that rat is subjected to the influence of Kaolin food ration in 3 days behind the rotatory stimulation.The rat motor disease is subjected to occur behind the rotatory stimulation differently to have a liking for the Kaolin behavior and make index with it, press the light and heavy degree of Kaolin food ration judgement motion sickness.
3. result
By table 3 as seen, compare with model control group, basic, normal, high dosage composition and middle and high dosage chlorphenamine maleate and dimenhydrinate can obviously suppress rat to be subjected to take in Kaolin behind the rotatory stimulation, and prompting compositions, chlorphenamine maleate and dimenhydrinate have better curative effect to the vomiting reaction of motion sickness.After the administration with administration before relatively, the middle and high dosage group of compositions no difference of science of statistics, and three dosage groups of chlorphenamine maleate and dimenhydrinate group there were significant differences statistically.The effect that the proof compositions suppresses the motion sickness vomiting reaction is better than chlorphenamine maleate and dimenhydrinate, can make the rat that is subjected to rotatory stimulation that the Kaolin food ration is kept normal level.
Table 3 is subjected to the reagent thing rat to be subjected to the influence (n=10) of Kaolin intake behind the rotatory stimulation
Annotate: compare with model control group:
*P＜0.05;
*P＜0.01; Compare after the administration with before the administration:
△P＜0.05;
△ △P＜0.01
Embodiment 16:
Influence to the mice autonomic activities
1. material
1.1 laboratory animal: Kunming mouse, male and female half and half, body weight 18～22g, the SPF level is provided by No.1 Military Medical Univ.'s Experimental Animal Center.
1.2 medicine and reagent dimenhydrinate; Chlorphenamine maleate; Caffeine; Compositions: combine by 50: 2 weight ratios by caffeine and chlorphenamine maleate.
1.3 instrument and equipment:
ZIL-2 type mice autonomic activities monitor, the institute of Materia Medica,Chinese Academy of Medical Sciences development.
2. method
Get 110 of Kunming mouses, be divided into 11 groups at random, it is the blank group, the dimenhydrinate group, chlorphenamine maleate low dose group (being equivalent to adult's clinical equivalent dosage 2mg/ time), dosage group in the chlorphenamine maleate (being equivalent to adult's clinical equivalent dosage 8mg/ time), chlorphenamine maleate high dose group (being equivalent to adult's clinical equivalent dosage 20mg/ time), caffeine low dose group (being equivalent to adult's clinical equivalent dosage 50mg/ time), dosage group in the caffeine (being equivalent to adult's clinical equivalent dosage 200mg/ time), caffeine high dose group (being equivalent to adult's clinical equivalent dosage 500mg/ time), compositions low dose group (being equivalent to adult's clinical equivalent dosage 52mg/ time), dosage group in the compositions (being equivalent to adult's clinical equivalent dosage 208mg/ time), compositions high dose group (being equivalent to adult's clinical equivalent dosage 520mg/ time), 10 every group.Before the administration, adopt ZIL-2 type mice autonomic activities monitor, animal is put into 4 camera bellows of monitor respectively, start the movable number of times of instrument record mice in 120s immediately, measured gastric infusion behind the 30min, press the movable number of times of said process replication mice in 120s in 30min, 60min, 120min, 180min after the administration, observe the influence of medicine spontaneous activity in mice.
3. result
By table 4 as seen, the basic, normal, high dosage group of compositions is compared before the autonomic activities number of times of each time point and administration after the administration, statistically there was no significant difference; Chlorphenamine maleate and dimenhydrinate can obviously reduce mice autonomic activities number of times; And caffeine can obviously increase mice autonomic activities number of times.The proof compositions does not produce obvious influence to the autonomic activities of mice.
Annotate: compare after the administration with before the administration:
*P＜0.05;
*P＜0.01.
Embodiment 17:
Influence (pole-climbing method) to the mice coordination exercise
1. material
1.1 the laboratory animal Kunming mouse, male and female half and half, body weight 18～22g, the SPF level is provided by No.1 Military Medical Univ.'s Experimental Animal Center.
1.2 medicine and reagent dimenhydrinate; Chlorphenamine maleate; Caffeine; Compositions: combine by 50: 2 weight ratios by caffeine and chlorphenamine maleate.
2. method
Get 110 of Kunming mouses, be divided into 11 groups at random, it is the blank group, the dimenhydrinate group, chlorphenamine maleate low dose group (being equivalent to adult's clinical equivalent dosage 2mg/ time), dosage group in the chlorphenamine maleate (being equivalent to adult's clinical equivalent dosage 8mg/ time), chlorphenamine maleate high dose group (being equivalent to adult's clinical equivalent dosage 20mg/ time), caffeine low dose group (being equivalent to adult's clinical equivalent dosage 50mg/ time), dosage group in the caffeine (being equivalent to adult's clinical equivalent dosage 200mg/ time), caffeine high dose group (being equivalent to adult's clinical equivalent dosage 500mg/ time), compositions low dose group (being equivalent to adult's clinical equivalent dosage 52mg/ time), dosage group in the compositions (being equivalent to adult's clinical equivalent dosage 208mg/ time), compositions high dose group (being equivalent to adult's clinical equivalent dosage 520mg/ time), 10 every group.Before the administration, smooth metal bar one end of diameter 1.27cm, a long 76.2cm is fixed on the table top, each group mice is placed on the top of bar one by one, head allows it creep naturally downwards downwards, and the record mice level score value of creeping downwards.Measured gastric infusion behind the 30min, the level score value that 60min, 120min, 180min creep by said process replication mice after administration downwards.Be subjected to of the influence of reagent thing with judgement to the mice coordination ability.
Coordination exercise level score value: 0 grade: creep downwards step by step; 1 grade: slide downwards; 2 grades: can not catch bar; 3 grades: righting reflex loss.Establish 0.5,1.5,2.5 grade at 0～3 inter-stage, experimental result is calculated with the level score value.
3. result
By table 5 as seen, compare before the coordination exercise level score value of the basic, normal, high dosage group of compositions and the basic, normal, high dosage group of caffeine each time point after administration and the administration, statistically there was no significant difference; And compare before level score value and the administration after administration of basic, normal, high dosage group of chlorphenamine maleate and dimenhydrinate group, has significant difference statistically, prompting chlorphenamine maleate and dimenhydrinate can obviously suppress the coordination exercise of mice, and compositions does not exert an influence to the coordination exercise of mice.
Annotate: compare after the administration with before the administration:
*P＜0.05;
*P＜0.01
Embodiment 18:
Influence to sub-threshold dose pentobarbital sodium syngignoscism
1. material
1.1 the laboratory animal Kunming mouse, male and female half and half, body weight 18～22g, the SPF level is provided by No.1 Military Medical Univ.'s Experimental Animal Center.
1.2 medicine and reagent dimenhydrinate; Chlorphenamine maleate; Caffeine; Compositions: combine by 50: 2 weight ratios by caffeine and chlorphenamine maleate; The pentobarbital sodium solution: get the pentobarbital sodium powder and be mixed with solution with normal saline respectively, standby.
2. method
By prerun, determine that the pentobarbital sodium maximum dose level that 100% mice righting reflex is not disappeared is 30mg/kg (ip.).Get 110 of Kunming mouses, be divided into 11 groups at random, it is the blank group, the dimenhydrinate group, chlorphenamine maleate low dose group (being equivalent to adult's clinical equivalent dosage 2mg/ time), dosage group in the chlorphenamine maleate (being equivalent to adult's clinical equivalent dosage 8mg/ time), chlorphenamine maleate high dose group (being equivalent to adult's clinical equivalent dosage 20mg/ time), caffeine low dose group (being equivalent to adult's clinical equivalent dosage 50mg/ time), dosage group in the caffeine (being equivalent to adult's clinical equivalent dosage 200mg/ time), caffeine high dose group (being equivalent to adult's clinical equivalent dosage 500mg/ time), compositions low dose group (being equivalent to adult's clinical equivalent dosage 52mg/ time), dosage group in the compositions (being equivalent to adult's clinical equivalent dosage 208mg/ time), compositions high dose group (being equivalent to adult's clinical equivalent dosage 520mg/ time), every group 10, male and female half and half.Behind each treated animal gastric infusion 30 minutes, with all mices 30mg/kg lumbar injection pentobarbital sodium according to dosage, the number of observing the righting reflex loss mice was carried out X 2 test respectively to its result.
3. result
By table 6 as seen, the sleep incidence rate of the basic, normal, high dosage group of compositions and blank group compare, statistically there was no significant difference; And the sleep incidence rate of basic, normal, high dosage group of chlorphenamine maleate and dimenhydrinate group and blank group are relatively, have significant difference statistically.Prompting chlorphenamine maleate and dimenhydrinate and pentobarbital sodium have synergism, can cause drowsinessly, and compositions and caffeine and pentobarbital sodium do not have synergism, do not cause drowsiness.
Table 6 is subjected to the influence (n=10) of reagent thing to sub-threshold dose pentobarbital sodium in mice righting reflex loss
Embodiment 19:
Influence to dosage pentobarbital sodium in mice sleep above threshold
1. material
1.1 the laboratory animal Kunming mouse, male and female half and half, body weight 18～22g, the SPF level is provided by No.1 Military Medical Univ.'s Experimental Animal Center.
1.2 medicine and reagent dimenhydrinate; Chlorphenamine maleate; Caffeine; Compositions: combine by 50: 2 weight ratios by caffeine and chlorphenamine maleate; The pentobarbital sodium solution: get the pentobarbital sodium powder and be mixed with solution with normal saline respectively, standby.
2. method
By prerun, determining to make the sleeping pentobarbital sodium lowest dose level of 100% mice is 45mg/kg (ip.).Get 110 of Kunming mouses, be divided into 11 groups at random, it is the blank group, the dimenhydrinate group, chlorphenamine maleate low dose group (being equivalent to adult's clinical equivalent dosage 2mg/ time), dosage group in the chlorphenamine maleate (being equivalent to adult's clinical equivalent dosage 8mg/ time), chlorphenamine maleate high dose group (being equivalent to adult's clinical equivalent dosage 20mg/ time), caffeine low dose group (being equivalent to adult's clinical equivalent dosage 50mg/ time), dosage group in the caffeine (being equivalent to adult's clinical equivalent dosage 200mg/ time), caffeine high dose group (being equivalent to adult's clinical equivalent dosage 500mg/ time), compositions low dose group (being equivalent to adult's clinical equivalent dosage 52mg/ time), dosage group in the compositions (being equivalent to adult's clinical equivalent dosage 208mg/ time), compositions high dose group (being equivalent to adult's clinical equivalent dosage 520mg/ time), every group 10, male and female half and half.30min behind each treated animal gastric infusion with all mices 45mg/kg lumbar injection pentobarbital sodium according to dosage, observes and respectively organizes mouse sleep time, and the result is carried out the t check.
3. result
By table 7 as seen, the mouse sleep time of the basic, normal, high dosage group of compositions and blank group compare, statistically there was no significant difference; The length of one's sleep of basic, normal, high dosage group of chlorphenamine maleate and dimenhydrinate group and blank group relatively can obviously prolong mouse sleep time; And the length of one's sleep of the basic, normal, high dosage group of caffeine and blank group are relatively, can obviously reduce mouse sleep time.Prompting chlorphenamine maleate and dimenhydrinate and pentobarbital sodium have synergism, can cause drowsiness; Caffeine and pentobarbital sodium have antagonism, cause the mice excitement; And compositions and pentobarbital sodium neither have synergism and it is drowsiness to cause, also do not have antagonism and cause the mice excitement.
Table 7 is subjected to the influence (n=10) of reagent thing to dosage pentobarbital sodium in mice sleep above threshold
Annotate: compare with the blank group:
*P＜0.05;
*P＜0.01.
Claims (6)
- One kind the treatment and the prevention motion sickness pharmaceutical composition, it is characterized in that: this pharmaceutical composition contains caffeine, two kinds of materials of chlorphenamine maleate.
- 2. pharmaceutical composition according to claim 1 is characterized in that: its preferred mass proportioning is: caffeine: chlorphenamine maleate=50: 2.
- 3. pharmaceutical composition according to claim 2 is characterized in that: its single taking dose caffeine 50～500mg, chlorphenamine maleate 2～20mg.
- 4. pharmaceutical composition according to claim 3 is characterized in that: it is caffeine 200mg, chlorphenamine maleate 8mg that its single is taken optimal dosage.
- 5. the preparation of making according to the described pharmaceutical composition of one of claim 1 to 4, it is characterized in that: its adjuvant is starch-containing, lactose, mannitol, calcium hydrogen phosphate, carboxymethyl starch or its salt and group substituent, dextrin, chitosan, polyvinylpyrrolidone, cellulose family and derivant thereof, polyethylene glycols, and wherein starch is starch, tapioca, soluble starch, pregelatinized Starch; Cellulose family can be methylcellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, microcrystalline Cellulose; Polyethylene glycols is Macrogol 200～20000.
- 6. the preparation of making according to the described pharmaceutical composition of one of claim 1 to 4 is characterized in that: adopt the slow controlled-release technology on the pharmaceutics to be prepared into the slow controlled release thing for the treatment of motion sickness caffeine and chlorphenamine maleate.
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| CN108498493A (en) * | 2017-02-27 | 2018-09-07 | 中国人民解放军第二军医大学 | Mecamylamine prevents motion sickness or the medical usage of vertigo |
| CN110772524A (en) * | 2019-12-11 | 2020-02-11 | 方科伟 | Pharmaceutical composition for treating motion sickness |
| CN111281874A (en) * | 2020-02-26 | 2020-06-16 | 中国人民解放军第二军医大学 | Diphenhydramine and caffeine compound composition, and pharmaceutical composition and application thereof |
| CN114712484A (en) * | 2022-03-14 | 2022-07-08 | 中山大学 | Application of neuropeptide S in preparation of medicine for preventing and treating motion sickness |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1241568C (en) * | 2003-11-24 | 2006-02-15 | 天津太平洋制药有限公司 | Compound paracetamol and chlorphenamine maleate slow releasing tablet and its preparation |
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2007
- 2007-02-14 CN CN200710026927A patent/CN101244064B/en active Active
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| CN108498493A (en) * | 2017-02-27 | 2018-09-07 | 中国人民解放军第二军医大学 | Mecamylamine prevents motion sickness or the medical usage of vertigo |
| CN110772524A (en) * | 2019-12-11 | 2020-02-11 | 方科伟 | Pharmaceutical composition for treating motion sickness |
| CN111281874A (en) * | 2020-02-26 | 2020-06-16 | 中国人民解放军第二军医大学 | Diphenhydramine and caffeine compound composition, and pharmaceutical composition and application thereof |
| CN114712484A (en) * | 2022-03-14 | 2022-07-08 | 中山大学 | Application of neuropeptide S in preparation of medicine for preventing and treating motion sickness |
| CN114712484B (en) * | 2022-03-14 | 2023-07-04 | 中山大学 | Application of neuropeptide S in preparation of medicine for preventing and treating motion sickness |
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| CN101244064B (en) | 2012-10-10 |
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