CN109350736A - Prevent and treat motion sickness, the drug of Meniere disease and the medical usage of atrial natriuretic peptide - Google Patents
Prevent and treat motion sickness, the drug of Meniere disease and the medical usage of atrial natriuretic peptide Download PDFInfo
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- CN109350736A CN109350736A CN201811100634.9A CN201811100634A CN109350736A CN 109350736 A CN109350736 A CN 109350736A CN 201811100634 A CN201811100634 A CN 201811100634A CN 109350736 A CN109350736 A CN 109350736A
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Abstract
This application discloses a kind of prevention and treatment motion sickness, the drug of Meniere disease and the medical usage of atrial natriuretic peptide, the drug includes the atrial natriuretic peptide and pharmaceutically acceptable carrier of prevention and treatment motion sickness effective dose.By the above-mentioned means, the application can play effective reference function in terms of prevention and treatment motion sickness, Meniere disease, and then effective drug effect may be further functioned as.
Description
Technical field
This application involves field of medical technology, more particularly to a kind of prevention and treatment motion sickness, the drug of Meniere disease and atrium
The medical usage of natriuretic peptide.
Background technique
Motion sickness betides the vehicles such as people's riding vehicle, ship or carries out space flight, aviation or navigation operation, receives different
When normal vestibular stimulation and/or abnormal vision stimulate, mainly have pale complexion, cold sweat, salivation, indifferent, abdominal discomfort, dizziness,
The neuro-vegetative responses such as Nausea and vomiting.Meniere disease be based on the rotatory vertigo that breaks out, and with tinnitus, deafness,
The symptoms such as sensation of fullness are a kind of disease of inner ear of main feature in head or ear, and the violent person of dizziness can be with Nausea and vomiting, cold sweat
Etc. symptoms.
Existing motion sickness resistant medicament is many kinds of, and the best single medicine of control efficiency is anticholinergic agent hyoscine at present,
And the most commonly used is antihistamine dramamine.Treatment for Meniere disease, at present mainly using anti-blooming, calmness, expansion blood vessel,
Dehydration and the remedy measures such as supporting treatment when conservative therapy is invalid, consider operative treatment, as endolymphatic sac decompression or bypass,
Neurotomy of vestibular nerve, lost damage or resection etc..
Present inventor has found in long-term R&D process, above-mentioned anti-kinetosis Common drugs side effect compared with
By force, especially the side effects such as CNS inhibition, eye-blurred will affect operation of the people under various special environment conditions.It is right simultaneously
It in the treatment method of Meniere disease, or influences whether therapeutic effect, or some hearing damages and vestibular function etc. can be brought
Serious side effect.Therefore, it is necessary to develop the drug of new prevention and treatment motion sickness and Meniere disease.
Summary of the invention
The application is mainly solving the technical problems that provide a kind of drug and atrial natriuretic for preventing and treating motion sickness, Meniere disease
The medical usage of peptide can play effective reference function in terms of prevention and treatment motion sickness, Meniere disease, and then may further serve as
To effective drug effect.
In order to solve the above technical problems, the technical solution that the application uses is: providing a kind of medicine for preventing and treating motion sickness
Object, the drug include the atrial natriuretic peptide and pharmaceutically acceptable carrier for preventing and treating motion sickness effective dose.
In order to solve the above technical problems, another technical solution that the application uses is: providing a kind of prevention and treatment Meniere disease
Drug, the drug include prevention and treatment Meniere disease effective dose atrial natriuretic peptide and pharmaceutically acceptable carrier.
In order to solve the above technical problems, another technical solution that the application uses is: providing a kind of atrial natriuretic peptide and exist
Prevent and treat the purposes in the medicine preparation of motion sickness.
In order to solve the above technical problems, another technical solution that the application uses is: providing a kind of atrial natriuretic peptide and exist
Prevent and treat the purposes in the preparation of the drug of Meniere disease.
The beneficial effect of the application is: being in contrast to the prior art, the application prevents and treats motion sickness/Meniere disease medicine
Object includes prevention and treatment motion sickness/Meniere disease effective dose atrial natriuretic peptide and pharmaceutically acceptable carrier.Wherein, atrium
Natriuretic peptide can play effective reference function in terms of prevention and treatment motion sickness, Meniere disease, and then may further function as effectively
Drug effect.
Detailed description of the invention
To describe the technical solutions in the embodiments of the present invention more clearly, make required in being described below to embodiment
Attached drawing is briefly described, it should be apparent that, drawings in the following description are only some embodiments of the invention, for
For those of ordinary skill in the art, without creative efforts, it can also be obtained according to these attached drawings other
Attached drawing.Wherein:
Fig. 1 is the signal that 5 groups of rats drink one embodiment of saccharin sodium solution reduction amount after arginine vasopressin injection
Figure；
Fig. 2 is the schematic diagram that 4 groups of rats drink one embodiment of saccharin sodium solution reduction amount after rotatory stimulation.
Specific embodiment
Below in conjunction with the attached drawing in the embodiment of the present application, technical solutions in the embodiments of the present application carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of embodiments of the present application, rather than whole embodiments.Based on this
Embodiment in application, those of ordinary skill in the art are obtained every other without making creative work
Embodiment shall fall in the protection scope of this application.
Firstly, simply introducing motion sickness and the relevant prior art scenario of Meniere disease.
Motion sickness betides the vehicles such as people's riding vehicle, ship or carries out space flight, aviation or navigation operation, receives different
When normal vestibular stimulation and/or abnormal vision stimulate, mainly have pale complexion, cold sweat, salivation, indifferent, abdominal discomfort, dizziness,
The neuro-vegetative responses such as Nausea and vomiting.For a long time, but its detailed pathogenesis is still not very clear for motion sickness research history,
Still lack efficient and without side-effects drug at present in terms of motion sickness prevention and treatment.There are many existing motion sickness resistant medicaments, but this
A little drug useful effect positions are unclear, and side effect is larger, and the especially side effects such as CNS inhibition, eye-blurred will affect people
Operation under various special environment conditions.
Meniere disease is the rotatory vertigo to break out, and is with symptoms such as sensations of fullness in tinnitus, deafness, head or ear
A kind of disease of inner ear of main feature, the violent person of dizziness can be with symptoms such as Nausea and vomiting, cold sweats.Meniere disease is ear nose
Larynx section common disease and frequently-occurring disease are fallen ill common with monaural.For many years the study found that Meniere disease and immune response, plant mind
Related through the factors such as dysfunction or infection, these factors or interference inner ear microvascular function cause capillary and vein to return
Stream is obstructed, or blocks ductus endolymphaticus, and endolymph fluid malabsorption causes labyrintine hydrops, and inner ear equilibrium function is caused to be lacked of proper care.
Meniere disease urgency of often falling ill is easily repeatedly otorhinolaryngologic difficult treatment.Treatment for Meniere disease, so far due to the cause of disease
Not yet get clear completely, at present clinic mainly for its pathophysiological process based on symptomatic treatment, using anti-blooming, calmness, expansion
The remedy measures such as blood vessel, dehydration and supporting treatment when conservative therapy is invalid, consider operative treatment: endolymphatic sac decompression or shunting
Art, neurotomy of vestibular nerve, lost damage or resection etc..These methods or therapeutic effect is influenced, or brought
The serious side effect such as unnecessary or even hearing damage and vestibular function.
Atrial natriuretic peptide provided herein can play effective use for reference in terms of prevention and treatment motion sickness, Meniere disease and make
With, by atrial natriuretic peptide exploitation at prevention and treatment motion sickness and Meniere disease drug, will have a good application prospect, promoting
Also there is fairly obvious social effect in terms of the healthy cause of the mankind.
Atrial natriuretic peptide (ANP), also known as atrial natriuretic peptide are the peptide hormone for being synthesized and being discharged by atrial muscle cell, people
ANP in blood circulation is made of 28 amino acid residues, and receptor is a kind of bird sweet acid cyclase on cell membrane.At present
The effect for the atrial natriuretic peptide known includes: to reduce blood pressure, sharp sodium, diuresis, adjust circulating blood volume, adjust cell Proliferation etc..
This application provides a kind of prevention and treatment motion sickness/Meniere disease drug, which includes prevention and treatment motion sickness/Andre Meynier
The atrial natriuretic peptide of sick effective dose and pharmaceutically acceptable carrier.
In one embodiment, prevention and treatment provided herein motion sickness/Meniere disease drug can pass through routine
Preparation process mixes with atrial natriuretic peptide pharmaceutically acceptable carrier to prepare the spy to be formed and be administered in a manner of non-oral routes
Determine the drug of dosage form.Above-mentioned dosage form includes: solid dosage forms (for example, crystallization, pulvis etc.) and liquid dosage form (for example, aqueous solution, mixed
Suspension, finish etc.).Above-mentioned non-oral routes include intravenous injection, intramuscular injection, subcutaneous injection etc., when above-mentioned dosage form is solid
When dosage form (for example, pulvis, crystallization etc.), the liquid such as drug and physiological saline or glucose can be mixed into after liquid to inject makes
With.
In an application scenarios, when dosage form is solid dosage forms, acceptable carrier includes: to assign on the application traditional Chinese medicine
Shape agent (for example, lactose, sucrose), binder (for example, water, ethyl alcohol, propyl alcohol, gelatin solution etc.), wetting agent are (for example, glycerol
Deng), lubricant (for example, stearate, boric acid powder, polyethylene glycol etc.) etc..
In another application scenarios, when dosage form is liquid dosage form, acceptable carrier includes: on the application traditional Chinese medicine
Diluent (for example, water, ethyl alcohol, propylene glycol, lactic acid aqueous solution etc.) etc..
Certainly, in other embodiments, other pharmaceutically acceptable carrier (examples can be also added according to the actual situation
Such as, pH buffer, emulsifier, pigment, dyestuff etc.), the application is not construed as limiting this.
In another embodiment, prevention and treatment provided herein motion sickness/Meniere disease drug is in dosage unit
Form.The dosage of the atrial natriuretic peptide contained in the drug of different dosage forms can be the same or different, the drug of same dosage form
In the dosage of atrial natriuretic peptide that contains can it is identical can also be different；For example, being all the drug of liquid dosage form, the atrium contained
The dosage of natriuretic peptide can be 30mg, be also possible to 60mg etc..
In an application scenarios, skilled medical practitioner can be easily according to the species of patient (for example, people, dog, orangutan
Deng), gender, weight, age, medical condition, administration route, the factors such as state of the illness, determining and regulation controls
Treat the effective dose of atrial natriuretic peptide in the drug of disease.In addition, the effective dose applied is with institute's method of application, required treatment
And indicated disease and change.Total daily dose can be applied with single dose or fractionated dose.For example, in adult's list
When the drug of secondary intravenous injection prevention and treatment motion sickness, the dosage of atrial natriuretic peptide is 30-60mg in drug, for example, 30mg, 40mg,
50mg, 60mg etc..
Listed dosage range is only illustrative in above-described embodiment, and dosage can be according to pharmacokinetics or drug effect
Parameter adjustment is learned, pharmacokinetics or pharmacodynamic parameter may include clinical effect such as toxic effect and/or laboratory evaluation.Cause
This, the application covers Intra-patient dose escalation determined by those skilled in the art.Determine the suitable agent of application atrial natriuretic peptide
Amount and scheme are known in the related art, and once provide religious doctrine disclosed herein, it should be understood that by the field
Technical staff covered.
The drug of the application can with bulk form, with single unit dosage form or with multiple single unit dosage forms
Preparation, packaging are sold." unit dose " used herein is the discrete amount of the drug of the atrial natriuretic peptide comprising predetermined amount.Atrium
The amount of natriuretic peptide will generally equal to be applied to the dosage of the atrial natriuretic peptide of subject or one of this dose easily divides
Number, for example, for example, a half or thirds of this dose.
The relative quantity of atrial natriuretic peptide, pharmaceutically acceptable carrier and any other ingredient is by root in the application drug
According to the identity of treated subject, size and situation and further changed according to the dosing way of composition.For example, group
Closing object may include the atrial natriuretic peptide between 0.1% and 100% (w/w).
Present invention also provides purposes of the above-mentioned atrial natriuretic peptide in prevention and treatment motion sickness/Meniere disease medicine preparation.
In one embodiment, which further comprises pharmaceutically acceptable carrier, about load in the present embodiment
The selection of body can be found in above-described embodiment, and details are not described herein.
In another embodiment, motion sickness/Meniere disease drug is prevented and treated in the application can further include one kind
Or it is various other for preventing and treating the effective drug of motion sickness/Meniere disease, the component of these drugs is in same preparation or single
For being administered simultaneously or being successively administered in only preparation.
It includes at least two active groups that motion sickness/Meniere disease drug is prevented and treated in an application scenarios, in the application
Point, respectively the first active component and the second active component, wherein the first active component is atrial natriuretic peptide；By the first active group
Point and carrier use conventional formulation technique to form the first preparation, by the second active component and carrier use conventional formulation technique with
The second preparation is formed, patient successively injects above-mentioned first preparation and the second preparation.In another application scenarios, by the first activity
Component, the second active component and carrier use conventional formulation technique to form third preparation, and patient injects above-mentioned third preparation.?
In another application scenarios, the effective dose ratio of above-mentioned first active component and the second active component is 1:1,2:1,1:2 etc., is somebody's turn to do
Effective dose ratio can be adjusted according to the actual situation by doctor, and the application is not construed as limiting this.
It is effectively borrowed with specific data to illustrate that atrial natriuretic peptide provides in terms of prevention and treatment motion sickness, Meniere disease below
Mirror effect.
The application has carried out the related arginine vasopressin in relation to atrial natriuretic peptide in terms of prevention and treatment motion sickness, Meniere disease
Stimulation, rotatory stimulation experimental study, it was confirmed that atrial natriuretic peptide has the function of explicitly preventing and treating motion sickness, Meniere disease, is
It provides more complete experimental basis as a kind of novel prevention and treatment motion sickness, the drug of Meniere disease and its clinical application.Under
Arrange it is each experiment be merely to illustrate atrial natriuretic peptide have the effect of prevent and treat motion sickness, Meniere disease, cannot be considered as to the application guarantor
Protect the limitation of range.
Specifically: carrying out (Sprague-Dawley, SD) rat with sprague and design for research object different to use pharmacopoeia
Class and dosage group carry out arginine vasopressin stimulation, rotatory stimulation experiment, to determine atrial natriuretic peptide to prevention and treatment motion sickness, plum
The sick effect of Buddhist nun angstrom.
Atrial natriuretic peptide used in following experiments is purchased from Britain's support Crius bioscience (Tocris Bioscience)
Company, arginine vasopressin are purchased from western trellis code-aldrich (Sigma-Aldrich) company of the U.S., hyoscine
(Scopolamine) it is produced then at medicine company limited liability company by Henan, SD rat is provided by Nantong University's Experimental Animal Center.
The influence of experiment 1, atrial natriuretic peptide to the conditioned taste aversion for inhibiting arginine vasopressin stimulation induction
Step 1: choosing 60 motion sickness Sensitive Rats, specific selection process is as follows: selection SD rat is several, and weight exists
200-220g, half male and half female adaptive feeding 3 days, then carry out motion sickness susceptibility screening test, repeat experiment one every other week
Secondary, two times result is consistent；By the 0.15% saccharin sodium solution amount of drinking in after rotatory stimulation 24 hours and before rotatory stimulation 48 small
The Shi Pingjun daily amount of drinking compares, and is considered that motion sickness is quick if the 0.15% saccharin sodium solution amount of drinking fall >=15%
Feel rat.
Step 2: 60 motion sickness Sensitive Rats are randomly divided into 5 groups, every group 12, it is respectively as follows: saline control
Group, arginine vasopressin (200 μ g/kg) stimulation group, atrial natriuretic peptide low dosage (200 μ g/kg) group, atrial natriuretic peptide high dose
(400 μ g/kg) group, hyoscine (80 μ g/kg) positive drug control group.
Step 3: comparative experiments, detailed process is as follows:, which starts to give one morning 0.15% saccharin sodium solution, allows 5 groups
Rat is freely drunk, to be familiar with, adapt to for 24 hours, regular supply drinking public water supply.The next morning continues to give 0.15% saccharin sodium
Solution, the third day morning, which continues to give 0.15% saccharin sodium solution, allows 5 groups of rats to drink again for 24 hours, and record each group rat is daily
The 0.15% saccharin sodium solution amount of drinking.The 4th day morning, with 1mL syringe through the correspondence group prepared in right amount by weight is injected intraperitoneally
Reagent, wherein saline control group, arginine vasopressin stimulation group, atrial natriuretic peptide low dose group, atrial natriuretic peptide are high
Dosage group, the corresponding reagent of hyoscine positive drug control group are respectively as follows: the physiological saline of 2ml/kg weight, 2ml/kg weight
Physiological saline, the atrial natriuretic peptide of 200 μ g/kg weight, the atrial natriuretic peptide of 400 μ g/kg weight, 80 μ g/kg weight east
Hyoscyamine, to arginine vasopressin stimulation group, atrial natriuretic peptide low dose group, atrial natriuretic peptide high dose group, east Liang after 30min
The 200 μ g/kg weight of rats by intraperitoneal injection arginine vasopressin of henbane alkali positive drug control group, that is, stimulate intracorporal pitressin V2
Receptor, the effect of simulation arginine vasopressin stimulation inner ear.It then proceedes to give 0.15% saccharin sodium solution, continues to remember within the 5th day
Record the 0.15% saccharin sodium solution amount of drinking of each group rat.
The amount of drinking for the 0.15% saccharin sodium solution that 48h is recorded before being injected according to above-mentioned arginine vasopressin, calculates
Then the average daily amount of drinking of every group of rat calculates what 1 day saccharin sodium solution amount of drinking after arginine vasopressin is injected was reduced
Percentage judges SD rat conditioned taste aversion degree that arginine vasopressin is induced and atrial natriuretic peptide various dose
It influences.
Referring to Fig. 1, Fig. 1 is that 5 groups of rats drink the implementation of saccharin sodium solution reduction amount one after arginine vasopressin injection
The schematic diagram of mode.Each group of data indicates that group difference uses the variance analysis of Group Design with mean ± standard error, compares two-by-two
It is examined compared with using Scheffe method (Scheffe)., it is apparent that after arginine vasopressin injection, it is big with saline control group
Mouse is compared, and the saccharin sodium solution amount of drinking of arginine vasopressin stimulation group rat significantly reduces (p < 0.05), and atrial natriuretic peptide is low
The inhibiting effect of dosage group is weaker, no significant (p > 0.05), and atrial natriuretic peptide high dose group rat saccharin sodium solution
The amount of drinking is obviously increased relative to arginine vasopressin group, and atrial natriuretic peptide high dose group is compared with arginine vasopressin group
Difference has significant (p < 0.05), this effect is similar with the result of hyoscine positive drug control group.This illustrates the heart
Room natriuretic peptide high dose group, which can significantly inhibit arginine vasopressin, stimulates induced SD rat conditioned taste aversion, and
This effect is suitable with the effect of positive control medicine hyoscine.
The influence of experiment 2, atrial natriuretic peptide to the conditioned taste aversion for inhibiting rotatory stimulation induction
Step 1: choosing 48 motion sickness Sensitive Rats, specific process of choosing is identical with above-mentioned experiment 1, herein no longer
It repeats.
Step 2: 48 motion sickness Sensitive Rats are randomly divided into 4 groups, every group 12, it is respectively as follows: saline control
Group, rotatory stimulation group, atrial natriuretic peptide high dose (400 μ g/kg) group, hyoscine (80 μ g/kg) positive drug control group.
Step 3: comparative experiments, have process as follows: the, which starts to give one morning 0.15% saccharin sodium solution, allows 4 groups
Rat is freely drunk, to be familiar with, adapt to for 24 hours, regular supply drinking public water supply.The next morning continues to give 0.15% saccharin sodium
Solution, the third day morning, which continues to give 0.15% saccharin sodium solution, allows 4 groups of rats to drink again for 24 hours, and record each group rat is daily
The 0.15% saccharin sodium solution amount of drinking.The 4th day morning, with 1mL syringe through the correspondence group prepared in right amount by weight is injected intraperitoneally
Reagent, wherein saline control group, rotatory stimulation group, atrial natriuretic peptide high dose group, hyoscine positive drug control
Group be respectively as follows: the physiological saline of 2ml/kg weight, the physiological saline of 2ml/kg weight, 400 μ g/kg weight atrial natriuretic peptide,
The hyoscine of 80 μ g/kg weight, rotatory stimulation group, atrial natriuretic peptide high dose group, hyoscine positive drug pair after 30min
Rotatory stimulation is carried out according to group rat.In this experiment, rotatory stimulation device is referring to Crampton (Crampton) and Lv Ke
(Lucot) report of (1985) is imitated.When carrying out rotatory stimulation experiment, SD rat is put into rotatory stimulation device chainlessly
In, it is rotated clockwise around trunnion axis, with 16 °/s2Angular acceleration accelerates, after reaching 120 °/s of maximum speed, immediately with -48 °/s2's
Angular acceleration slows down, until rotation stops being a cycle, lasts 10s.Then, opposite direction repetitive stimulation.It stimulates repeatedly
2h.It then proceedes to give 0.15% saccharin sodium solution, continues within the 5th day the saccharin sodium solution amount of drinking for recording each group SD rat.
According to the amount of drinking of the 0.15% saccharin sodium solution recorded of 48h before above-mentioned rotatory stimulation, every group of rat is calculated
Then the average daily amount of drinking calculates the percentage of the saccharin sodium solution amount of drinking reduction in 1 day after rotatory stimulation, judge rotation thorn
Swash the influence of induced SD rat conditioned taste aversion degree and atrial natriuretic peptide.
Referring to Fig. 2, Fig. 2 is that 4 groups of rats drink showing for one embodiment of saccharin sodium solution reduction amount after rotatory stimulation
It is intended to.Each group of data indicates that group difference uses the variance analysis of Group Design with mean ± standard error, compares two-by-two using Xue
Take method (Scheffe) inspection., it is apparent that after rotatory stimulation, compared with saline control group rat, rotatory stimulation group
The saccharin sodium solution amount of drinking of rat significantly reduces (p < 0.01), and atrial natriuretic peptide high dose group rat saccharin sodium solution is drunk
Amount is obviously increased relative to rotatory stimulation group, and atrial natriuretic peptide high dose group and rotatory stimulation group comparing difference have conspicuousness
Meaning (p < 0.05), this effect are similar with the result of hyoscine positive drug control group.This illustrates the high agent of atrial natriuretic peptide
Amount group can significantly inhibit the SD rat conditioned taste aversion that rotatory stimulation is induced, and this effect and positive control drug
The effect of object hyoscine is suitable.
The application has carried out related to rotatory stimulation in the arginine vasopressin stimulation of rat model in relation to atrial natriuretic peptide
Experimental study, it was confirmed that atrial natriuretic peptide be able to suppress rotatory stimulation and arginine vasopressin stimulation induction rat conditionity
Taste aversion has provided for it as a kind of novel prevention and treatment motion sickness, the drug for the treatment of Meniere disease and its clinical application
Whole experimental basis.Therefore, the drug for atrial natriuretic peptide being developed into prevention and treatment motion sickness and being treated Meniere disease, will have good
Good application prospect also has fairly obvious social effect in terms of the healthy cause for promoting the mankind.
Mode the above is only the implementation of the present invention is not intended to limit the scope of the invention, all to utilize this
Equivalent structure or equivalent flow shift made by description of the invention content is applied directly or indirectly in other relevant technology necks
Domain is included within the scope of the present invention.
Claims (10)
1. a kind of drug for preventing and treating motion sickness, which is characterized in that the drug includes the atrium sodium of prevention and treatment motion sickness effective dose
Urinate peptide and pharmaceutically acceptable carrier.
2. drug according to claim 1, which is characterized in that the drug is in dosage unit form.
3. drug according to claim 1, which is characterized in that the drug is prepared using conventional formulation technique
The preparation that non-oral routes mode is administered.
4. a kind of drug for preventing and treating Meniere disease, which is characterized in that the drug includes the heart of prevention and treatment Meniere disease effective dose
Room natriuretic peptide and pharmaceutically acceptable carrier.
5. drug according to claim 4, which is characterized in that the drug is in dosage unit form.
6. drug according to claim 4, which is characterized in that the drug is prepared using conventional formulation technique
The preparation that non-oral routes mode is administered.
7. a kind of purposes of atrial natriuretic peptide in the medicine preparation of prevention and treatment motion sickness.
8. purposes according to claim 7, which is characterized in that
The drug further includes one or more other medicines for preventing and treating motion sickness, and the component of the drug is identical
It is used in preparation or in independent preparation be administered either simultaneously or sequentially.
9. a kind of purposes of atrial natriuretic peptide in the medicine preparation of prevention and treatment Meniere disease.
10. purposes according to claim 9, which is characterized in that the drug is further included for preventing and treating Meniere disease
One or more other medicines, the component of the drug is in same preparation or in independent preparation for simultaneously or sequentially
Administration.
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| CN1142816A (en) * | 1993-12-04 | 1997-02-12 | 辉瑞研究及发展公司 | Crystalline, polymorphic form of (S,S,S)-n-(1-[2-carboxy-3-(n2-mesyllysylamino)propyl]-1-cyclopenlylcarbonyl)tyrosine |
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| WARREN LOCKETTE ET AL.: ""Atrial Natriuretic Factor Increases Vascular Permeability", 《AVIATION,SPACE,AND ENVURONMENTAL MEDICINE》 * |
| 侯建萍等: "防晕船口服液对晕船患者血管加压素及胃泌素的影响", 《中华航海医学与高气压医学杂志》 * |
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