CN107252426A - Application of the dexchlorpheniramine in anti-motion sickness field - Google Patents
Application of the dexchlorpheniramine in anti-motion sickness field Download PDFInfo
- Publication number
- CN107252426A CN107252426A CN201710611678.7A CN201710611678A CN107252426A CN 107252426 A CN107252426 A CN 107252426A CN 201710611678 A CN201710611678 A CN 201710611678A CN 107252426 A CN107252426 A CN 107252426A
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- CN
- China
- Prior art keywords
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- dexchlorpheniramine
- motion sickness
- oral liquid
- chlorphenamine
- Prior art date
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- Pending
Links
- 201000003152 motion sickness Diseases 0.000 title claims abstract description 39
- 229960001882 dexchlorpheniramine Drugs 0.000 title claims abstract description 37
- SOYKEARSMXGVTM-HNNXBMFYSA-N dexchlorpheniramine Chemical compound C1([C@H](CCN(C)C)C=2N=CC=CC=2)=CC=C(Cl)C=C1 SOYKEARSMXGVTM-HNNXBMFYSA-N 0.000 title claims abstract description 36
- 239000003814 drug Substances 0.000 claims abstract description 40
- 238000002360 preparation method Methods 0.000 claims description 35
- 239000007921 spray Substances 0.000 claims description 32
- 239000000203 mixture Substances 0.000 claims description 20
- 239000007788 liquid Substances 0.000 claims description 19
- 238000009472 formulation Methods 0.000 claims description 17
- 229960000520 diphenhydramine Drugs 0.000 claims description 16
- 229940079593 drug Drugs 0.000 claims description 16
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 15
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 claims description 14
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- 229960002646 scopolamine Drugs 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 8
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 8
- 239000003826 tablet Substances 0.000 claims description 8
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 239000007937 lozenge Substances 0.000 claims description 6
- -1 patch Substances 0.000 claims description 6
- 229940112822 chewing gum Drugs 0.000 claims description 5
- 235000015218 chewing gum Nutrition 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 claims description 3
- OCJYIGYOJCODJL-UHFFFAOYSA-N Meclizine Chemical compound CC1=CC=CC(CN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC(Cl)=CC=2)=C1 OCJYIGYOJCODJL-UHFFFAOYSA-N 0.000 claims description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 239000007910 chewable tablet Substances 0.000 claims description 3
- DERZBLKQOCDDDZ-JLHYYAGUSA-N cinnarizine Chemical compound C1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1C\C=C\C1=CC=CC=C1 DERZBLKQOCDDDZ-JLHYYAGUSA-N 0.000 claims description 3
- 229960000876 cinnarizine Drugs 0.000 claims description 3
- 229960003564 cyclizine Drugs 0.000 claims description 3
- UVKZSORBKUEBAZ-UHFFFAOYSA-N cyclizine Chemical compound C1CN(C)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 UVKZSORBKUEBAZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000007938 effervescent tablet Substances 0.000 claims description 3
- 229960001474 meclozine Drugs 0.000 claims description 3
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- 239000000725 suspension Substances 0.000 claims description 3
- 229940095064 tartrate Drugs 0.000 claims description 3
- 229950004288 tosilate Drugs 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 150000003891 oxalate salts Chemical class 0.000 claims description 2
- 239000003182 parenteral nutrition solution Substances 0.000 claims description 2
- 239000002245 particle Substances 0.000 claims 1
- 150000003016 phosphoric acids Chemical class 0.000 claims 1
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 claims 1
- 230000002265 prevention Effects 0.000 abstract description 14
- 230000000694 effects Effects 0.000 description 45
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 34
- 229960003291 chlorphenamine Drugs 0.000 description 31
- 238000012360 testing method Methods 0.000 description 18
- LACQPOBCQQPVIT-SEYKEWMNSA-N scopolamine hydrobromide trihydrate Chemical compound O.O.O.Br.C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 LACQPOBCQQPVIT-SEYKEWMNSA-N 0.000 description 13
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- 241001465754 Metazoa Species 0.000 description 9
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- 206010041349 Somnolence Diseases 0.000 description 7
- 206010028813 Nausea Diseases 0.000 description 6
- 230000004438 eyesight Effects 0.000 description 6
- 230000008693 nausea Effects 0.000 description 6
- WYMSBXTXOHUIGT-UHFFFAOYSA-N paraoxon Chemical compound CCOP(=O)(OCC)OC1=CC=C([N+]([O-])=O)C=C1 WYMSBXTXOHUIGT-UHFFFAOYSA-N 0.000 description 6
- 208000009205 Tinnitus Diseases 0.000 description 5
- 206010047700 Vomiting Diseases 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- WTGQALLALWYDJH-MOUKNHLCSA-N scopolamine hydrobromide (anhydrous) Chemical compound Br.C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 WTGQALLALWYDJH-MOUKNHLCSA-N 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 231100000886 tinnitus Toxicity 0.000 description 5
- RKETZVBQTUSNLM-UHFFFAOYSA-N 6-(3-bromophenyl)-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole Chemical compound BrC1=CC=CC(C2N=C3SCCN3C2)=C1 RKETZVBQTUSNLM-UHFFFAOYSA-N 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 239000012669 liquid formulation Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
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- 238000003756 stirring Methods 0.000 description 4
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- 229960005372 dexchlorpheniramine maleate Drugs 0.000 description 3
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- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 3
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- 231100000869 headache Toxicity 0.000 description 3
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- CIVCELMLGDGMKZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC(Cl)=C(C(O)=O)C(Cl)=N1 CIVCELMLGDGMKZ-UHFFFAOYSA-N 0.000 description 2
- VSKJLJHPAFKHBX-UHFFFAOYSA-N 2-methylbuta-1,3-diene;styrene Chemical compound CC(=C)C=C.C=CC1=CC=CC=C1.C=CC1=CC=CC=C1 VSKJLJHPAFKHBX-UHFFFAOYSA-N 0.000 description 2
- NFLLKCVHYJRNRH-UHFFFAOYSA-N 8-chloro-1,3-dimethyl-7H-purine-2,6-dione 2-(diphenylmethyl)oxy-N,N-dimethylethanamine Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC(Cl)=N2.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 NFLLKCVHYJRNRH-UHFFFAOYSA-N 0.000 description 2
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- 239000007864 aqueous solution Substances 0.000 description 2
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 229960001803 cetirizine Drugs 0.000 description 2
- 239000000544 cholinesterase inhibitor Substances 0.000 description 2
- 229960000525 diphenhydramine hydrochloride Drugs 0.000 description 2
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- 239000007924 injection Substances 0.000 description 2
- 230000000116 mitigating effect Effects 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 2
- 229960002695 phenobarbital Drugs 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
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- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 description 1
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- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
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- 238000001949 anaesthesia Methods 0.000 description 1
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- 238000010171 animal model Methods 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
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- 239000000739 antihistaminic agent Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
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- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
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- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 1
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- FBUKVWPVBMHYJY-UHFFFAOYSA-M nonanoate Chemical compound CCCCCCCCC([O-])=O FBUKVWPVBMHYJY-UHFFFAOYSA-M 0.000 description 1
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
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- DAJSVUQLFFJUSX-UHFFFAOYSA-M sodium;dodecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCCCCS([O-])(=O)=O DAJSVUQLFFJUSX-UHFFFAOYSA-M 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to new application of the medicine dexchlorpheniramine in field of medicaments.In particular it relates to application of the dexchlorpheniramine (structural formula I) in terms for the treatment of, prevention or alleviation motion sickness.
Description
Technical field
This disclosure relates to new application of the medicine dexchlorpheniramine in field of medicaments.Specifically, dexchlorpheniramine
Or new application of its esters in terms for the treatment of, prevention or alleviation motion sickness.
Background technology
Motion sickness (motion sickness) is due to a kind of dizziness, nausea caused by passive movement (motion), vomitted
Tell, the malaise symptoms such as tinnitus.Humans and animals can all occur this when undergoing non-familiar or non-subjective form motion or relative motion
Symptom.Its pathogenesis is unclear, but generally believes to be due to that vestibular labyrinth, vision mutually conflict and caused with body-sensing system
(Brainard et al,Am Fam Physician.2014,90(1),41-46)；Brandt and Daroff,Ann
Neurol 1980,7,195-203.).The common form of expression has carsick, seasick, airsick and due to being shaken caused by a variety of causes
Vertigo caused by putting, jolt, rotating, accelerating etc..Symptom often by bus, navigation, several minutes of flight and other operations to
Occur after a few hours.It is embodied in epigastric discomfort, nausea, pale, cold sweat, dizziness, mental depression, salivary secretion increasing
Many and vomiting.China is one of country of motion sickness rate occurred frequently (Klosterhalfen et al, Aviat Space in the world
Environ Med 2005,76,1051-1057).The people that China is up to 80% once lived through different degrees of cinetosis reaction
(Zhuo Jiexian,《Liuzhou Journal of Teachers College》2007,22(3),123-126).Wherein, women and child's (2-12 Sui), pregnant woman, menstrual period woman
The ratio highest of motion sickness occurs for female, migraineur, about 5-10% crowd have serious motion sickness reaction (Money,
Physio Rev 1970,50,1-39)。
Although people are to the treatment of motion sickness, prevention or alleviate the research carried out widely, for motion sickness
The mechanism of generation does not still study clear, at present still without the method especially effectively cured.Use some anti-blooming medicines pair
Prevention alleviates motion sickness related symptoms and has certain curative effect, but be due to during these medicine uses individual difference compared with
Greatly, side effect substantially causes its utilization rate not high.In the world common cinetosis disease drug it is main with histamine receptor antagonists and
Based on the class medicine of nachr antagonist two.Some histamine receptor antagonists such as diphenhydramine, Cyclizine, meclozine is different
Promazine, cinnarizine etc. all has certain anti-motion sickness effect, and other antihistamine drugs (such as cetirizine, fexofenadine)
To preventing or alleviating motion sickness but without obvious effect (Cheung et al, Ann Pharmacother 2003,37,173-
7).Nachr antagonist (such as hyoscine, benzene ring pelargonate) can antagonism choline m receptor so as to mitigating by lost, vision and
The illusion of the uncoordinated generation of body-sensing system, promotion shake down, and play a part of alleviating and preventing motion sickness.Due to positioned at indigo plant
Noradrenergic neuron system in spot is suppressed by this neural false sense signal, and some sympathetic or sympathomimetics are refreshing
Antagonism or this inhibitory action can be reversed so as to anti-motion sickness effect through medicine.Anti-blooming in the market moves disease drug
(such as hyoscine, diphenhydramine, fenazil etc.) generally existing curative effect is unstable, and the obvious (Wood of calm, headache side effect
et al,Aviat Space Environ Med 1984,55(2),113– 116).Other emesis medicine such as serotonins
(5-HT3) receptor antagonist, neuropeptide NK1 receptor antagonists, prevention or slow of dopamine (D2) receptor antagonist to motion sickness
The effect of solution is more undesirable.
Chlorphenamine (chlorphenamine) belongs to first generation antihistamine H1 medicines, is most widely used medicine in the world
One of thing.Its purposes includes Reduce allergy symptom (by antagonism H1 acceptors), such as schneiderian membrance inflammation, nettle rash, eczema, dermatitis, coughs
Cough, drug rash, cutaneous pruritus, neurodermatitis, insect bite disease, solar dermatitis etc..Chlorphenamine maleate has water solubility
Fabulous (>25 DEG C of 160mg/mL at), Oral Gastrointestinal Tract absorbs good, rapid-action, Half-life in vivo length, better tolerance, secondary makees
The advantages of using small.Chinese invention patent CN200710026927.2 description using caffeine-chlorphenamine combination dosage forms rabbit,
The effect of the similar symptom of anti-motion sickness is shown in mouse animal experiment.Chinese invention patent CN201510625710.8 descriptions use east
Hyoscyamine-chlorphenamine, hyoscine-diphenhydramine, or the combined dosage form of hyoscine-(left side)-cetirizine composition have
Reduction subject produces the effect of motion sickness after being turn-taked on electronic chair.But the studies above is all using chlorphenamine and other
The combination preparation of medicine, and whether there is effect all not test, and existing for the carsick or seasick of human body
Anti-blooming moves agent and often there is the side effect such as drowsiness, dry, weak, and introducing other medicines are then readily incorporated new for anti-motion sickness
The combination of side effect, such as caffeine and chlorphenamine may bring digestive discomfort, constipation, diarrhoea, Nausea and vomiting, maincenter god
Stimulated through system, the side effect such as palpitating speed.Therefore, move agent for single component, high efficiency, low side effects of anti-blooming and still have
Demand, moving agent for the higher anti-blooming of activity in addition, there is also demand.
The chemical constitution of chlorphenamine is with an asymmetric carbon atom, with optical isomer.Applicant is first using the right side
Rotation chlorphenamine and to find that it has to motion sickness caused by riding vehicle, ship, aircraft and other similar jerky motions non-
Often good prevention and mitigation.The multiple formulations of dexchlorpheniramine, multiple dosage are directly used in carsick, seasick suffer from by the disclosure
Person simultaneously proves that it has significant curative effect, and prevention, treatment or the good result for alleviating motion sickness is fully achieved using its folk prescription.Mesh
It is preceding to be also used for motion sickness prevention or therapy field without document report dexchlorpheniramine.
The content of the invention
Main contents of the present invention include by dexchlorpheniramine medicinal application in prevention, alleviate or treat due to riding vehicle,
Ship, aircraft or other by motion sickness caused by jerky motion or relative motion.Anti-blooming in the market moves disease drug effect
Not good and side effect that is being difficult to receive causes utilization rate relatively low, motion sickness patient expect very much a kind of effect more preferably, side effect more
Small medicine is to alleviate, prevent and treat this malaise symptoms.Chlorphenamine is a kind of antiallergy generally used, alleviates flu
Symptom medicine, its side effect is relatively low, and tolerance is preferable, and most people had been used.The disclosure is right by active ingredient
Chlorphenamine monomer applications are revolved in the prevention of motion sickness, treatment or are alleviated, and find its antimotion sickness drug thing tool more existing than in the market
There are preferable anti-blooming effect and relatively low side effect.Compared with chlorphenamine raceme, the anti-motion sickness effect of dexchlorpheniramine
Significantly improve, but side effect is but unexpectedly without proportional increase.Clinical use can be substantially reduced using dexchlorpheniramine
Amount, while reducing the side effect that high dose medication is brought.
In one aspect, this disclosure relates to preparation for treating, preventing or alleviating motion sickness, wherein the preparation contains
The structural formula I of effective dose dexchlorpheniramine or its pharmaceutically acceptable salt
Structural formula I.
On the other hand, this disclosure relates to structural formula I dexchlorpheniramine or its salt prepare be used to treating, prevent or
Alleviate the purposes in the preparation of motion sickness.
Structural formula I.
According to any preceding aspect, wherein the preparation is only containing the dexchlorpheniramine of effective dose or its is pharmaceutically acceptable
Salt as anti-motion sickness active component.
According to any preceding aspect, wherein the preparation can also contain other active components.
According to any preceding aspect, wherein the preparation also contains pharmaceutical carrier or excipient.
According to any preceding aspect, wherein the pharmaceutically acceptable salt is selected from hydrochloride, sulfate, phosphate, horse
Come hydrochlorate, oxalates, citrate, tartrate, mesylate, tosilate, benzoate, acetate, be preferably
Maleate.
According to any preceding aspect, wherein the formulation of the preparation can be tablet, oral liquid, capsule, granule, note
Penetrate the molten film of liquid, patch, paste, lozenge, lozenge, chewable tablets, mouth, effervescent tablet, suspension, chewing gum, preferably oral liquid or
Chewing gum.
According to any preceding aspect, wherein the preparation also moves disease drug containing other anti-blooming, the medicine is selected from：Eastern Liang
Henbane alkali, diphenhydramine, Cyclizine, meclozine, fenazil, cinnarizine.
According to any preceding aspect, wherein the concentration of the oral liquid is 0.5-50mg/ml, preferably 1-20mg/ml is more excellent
Select 1-10mg/ml, such as 1.25,2.5,5,10mg/ml, the consumption of wherein patch is 4mg-50mg/ patches, preferably 4mg-
10mg/ is pasted, and wherein the consumption of spray sprays for 0.5mg-10mg/, preferably 1mg -5mg/ sprays.
Embodiment
Dexchlorpheniramine described in the disclosure refers to following structural formula I dexchlorpheniramine
Structural formula I.
It will be appreciated by those skilled in the art that the water that the disclosure is used can be water for injection, distilled water or distilled water etc., root
It can be carried out according to specific needs specifically chosen.
The preparation is only meaned containing the dexchlorpheniramine of effective dose or its pharmaceutically acceptable salt as active component
In dexchlorpheniramine preparation in addition to necessary solvent, auxiliary material or excipient, not containing other has pharmaceutical activity
Composition.
Dexchlorpheniramine or its pharmaceutically acceptable salt can be hydrochloride, sulfate, phosphate, maleate, grass
Hydrochlorate, citrate, tartrate, mesylate, tosilate, benzoate, acetate.
In one embodiment, dexchlorpheniramine or its pharmaceutically acceptable salt can be with them in the preparation of the disclosure
The composition that he has pharmaceutical activity is used cooperatively together.
In one embodiment, the preparation of the disclosure is the water-soluble of dexchlorpheniramine or its pharmaceutically acceptable salt
Liquid.The concentration of the aqueous solution is 0.5-50mg/ml, preferably 1-20mg/ml, more preferably 1-10mg/ml, such as 1.25,2.5,
5、10mg/ml.The aqueous solution can be oral liquid or parenteral solution.
In another embodiment, the preparation of the disclosure is the spray agent of dexchlorpheniramine maleate, described
Spray agent contains dexchlorpheniramine or its pharmaceutically acceptable salt, water, menthol.The spray, which is used, carries metered dose
The device administration of valve.The device with metered dose valve can be arranged to 0.1mg-50mg/ sprays, preferably 0.5mg-
10mg/ sprays, such as 0.5mg/ sprays, 1.25mg/ sprays, 2.5mg/ sprays, 5mg/ sprays.Device with metered dose valve can be commercially available
Product, it would however also be possible to employ voluntarily assemble, as long as the effect of metered dose can be realized.
In another embodiment, the preparation of the disclosure is transdermal paste preparation (or being transdermal patch), described transdermal
Paste preparation contains dexchlorpheniramine or its pharmaceutically acceptable salt and pharmaceutical carrier or excipient, wherein the carrier or figuration
Agent can be styrene-isoprene-phenylethene polymer.
In one embodiment, the formulation application of the disclosure is uncomfortable in the motion that ride-on vehicles are brought, and such as nausea, vomits
Tell, dizziness, dim eyesight, the symptom such as tinnitus.
In one embodiment, the formulation application of the disclosure such as nausea, is vomitted in taking the motion discomfort that ship is brought
Tell, dizziness, dim eyesight, the symptom such as tinnitus.
In one embodiment, the formulation application of the disclosure is uncomfortable in the motion that airplane is brought, and such as nausea, vomits
Tell, dizziness, dim eyesight, the symptom such as tinnitus.
In one embodiment, the formulation application of the disclosure such as nausea, is vomitted in the discomfort for being in movement environment and triggering
Tell, dizziness, dim eyesight, the symptom such as tinnitus.
Inventor is random long to 24 from dexchlorpheniramine, raceme chlorphenamine, hyoscine and diphenhydramine
Way bus totally 802 volunteers (having carsickness/ship custom) and to 4 times seagoing vessels totally 486 passenger volunteers's (thering is carsickness/ship to be accustomed to)
Tested, as a result show that the anti-blooming car (table 2) and anti-blooming ship (table 3) efficiency of dexchlorpheniramine are up to 96% He respectively
93%, the anti-blooming car and anti-blooming ship efficiency highest of racemization chlorphenamine are respectively 86% and 78%, the anti-blooming car of hyoscine and
Anti-blooming ship efficiency is respectively 88% and 80%, and the anti-blooming car and anti-blooming ship efficiency of diphenhydramine are respectively 89% and 81%, and empty
The anti-blooming car and anti-blooming ship efficiency of white reference substance (G/W) are respectively 13% and 0%.
Embodiment
Embodiment 1
The preparation of oral liquid formulations
Under gmp conditions, weighing 100g (or 50g, or 25g, or 12.5g) chlorphenamine maleate, (dextrorotation is corresponding
Raceme) be dissolved in 10L waters for injection, stirring is thoroughly dissolved until all medicines for 2 hours, molten into fully transparent clarification
Liquid, sterilization 15 minutes is carried out by 10L solution at 85 DEG C, be cooled to after room temperature carry out it is filling into 10000 vial formulations, every bottle of appearance
Measure as 1mL, containing 10mg (or 5mg, or 2.5mg, or 1.25mg) chlorphenamine (dextrorotation or corresponding raceme), ultimate density is
10mg/mL (or 5mg/mL, or 2.5mg/mL, or 1.25mg/mL).
Embodiment 2
The preparation of spray formu
Under gmp conditions, weigh 1250g chlorphenamines maleate (dextrorotation or corresponding raceme) and be dissolved in 10L steamings
In distilled water, then 5g menthols are weighed, stirring is placed at 85 DEG C and sterilized until being completely dissolved into transparent settled solution for 2 hours
Sterilization 15 minutes, is cooled to and carries out filling into 10000 bottles of spray agents for carrying metered dose valve after room temperature, every bottle of capacity is
1mL, chlorphenamine containing 125mg, spraying proportional valve often sprays once to be sprayed 1 time for 10 μ L (0.01mL), or 1.25mg/, 2.5mg/ sprays
2 times, 5mg/ sprays 4 times.
Embodiment 3
The preparation of transdermal paste preparation
Weigh 2kg styrene-isoprene-phenylethenes polymer and dissolved as being heated to 120 DEG C in blender jar, under stirring
Add azone (100g) solution of 50g (or 100g) chlorphenamines maleate (dextrorotation or its raceme), dodecyl
Sodium sulfonate (5g), stirs, and is cooled to 80 DEG C, is equably coated on adherent layer, is cooled to 30 DEG C or so, by back sheet lid
On, 10000 pieces, every piece 1cm x 2cm transdermal patch is cut into, every piece of patch contains chlorphenamine (dextrorotation or its raceme) 5mg
(or 10mg).The strata ester diaphragm embossed film layer of surface one is thrown off when using, skin surface is pasted on.
Embodiment 4
Selection rabbit determines test medicine and suppresses reverse activity test of turn-taking.Trial drug or physiological saline (blank) are existed
First 30 minutes are modeled by oral, transdermal or injection intake animal body, reference literature method (Lee more etc., China airlines
Aerospace medicine magazine 2006,17 (2)：87-91) set up animal model.By rabbit (1.9-2.5kg) with 2% procaine
Local anaesthesia, with acetylcholinesteraseinhibitors inhibitors paraoxon (the p-nitrophenyl diethylphosphate for wiping 10 μ L3.8% of lens paper absorption
Ester, Paraoxon) penetrate into blood from total arteries.As a result show control group (physiological saline group) small to paraoxon medicine 2
When interior animal all there are mandatory counter-rotating movements and (show the positive body that 3 circles/more than min is reverse syndrome of turn-taking
Levy), testing drug group and control medicine group all occur in that different degrees of suppression animal counter-rotating effect (table 1).It is normal dynamic
Thing (blank control group) is without reverse phenomenon of turn-taking is found, the animal for taking acetylcholinesteraseinhibitors inhibitors paraoxon group all goes out
Phenomenon of now inversely turn-taking (inhibiting rate 0%), is injected, oral, transdermal or schneiderian membrane is inputted before using paraoxon modeling to animal
After dexchlorpheniramine maleate and raceme chlorphenamine maleate, the phenomenon that animal inversely turn-takes is by different degrees of
Suppression, and this inhibitory action is related to dosage (identical method of administration contrast).Two positive control medicine hyoscine hydrogen
Bromate and diphenhydramine hydrochloride also show obvious degeneration-resistant to activity of turn-taking.The wherein suppression of scopolamine hydrobromide
System inversely turn-takes activity than dexchlorpheniramine maleic acid salt error, but than corresponding raceme chlorphenamine maleate slightly
By force.But side effect (the pupil increase of such as animal, drowsiness, vomiting that the animal in scopolamine hydrobromide group shows
Deng) apparently higher than dexchlorpheniramine maleate and raceme chlorphenamine maleate group.The suppression of diphenhydramine hydrochloride
It is active bright also aobvious less than corresponding dexchlorpheniramine maleate group and raceme chlorphenamine that braking thing is inversely turn-taked
Maleate group.
The chlorphenamine of table 1. is inversely turn-taked the result of syndrome to prevention rabbit
* P ＜ 0.001, P ＜ 0.05 show that difference has statistical significance
Embodiment 5
24 long-distance buses are selected, each formulation is carried out is administered test to the volunteer of 2 cars, and 802 have dizzy altogether
The volunteer of car history has participated in random test.Tester is volunteered in upper Chinese herbaceous peony intake in 30 minutes (oral, mucous membrane of mouth, transdermal patch)
Test medicine, drugs compared or blank (50% D/W), range of driving 6-7 hours.In order to obtain more accurately
Aspiration tester on data, same coastiong takes same medicine or blank control water.Wherein dexchlorpheniramine is tested
4 kinds of oral liquids (1.25mg, 2.5mg, 5mg, 10 mg), 2 kinds of mouthspray formulation (spray I：1.25mg/ sprays, spray II：
2.5mg/ sprays), 2 kinds of Transdermal patch dosage forms (patch I：5mg/ is pasted, patch II：10mg/ is pasted)；Raceme chlorphenamine tests a kind
Oral liquid (10mg), a kind of mouthspray formulation (spray R：5mg/ sprays), a kind of Transdermal patch dosage forms (patch R：10mg/ is pasted)；It is a kind of
Hyoscine tablet (" the phenobarbital Scopolamine Hydrobromide Tablets " of Guangzhou BaiYunshan GuangHua Pharmacy Co., Ltd's production：Every contains
Scopolamine hydrobromide 0.2mg)；A kind of diphenhydramine tablet (" dramamine of Shanghai Jinshan pharmaceutical Co., Ltd.'s production
Piece "：Every contains diphenhydramine 50mg)；A kind of blank control liquid (D/W 10mL), altogether 14 kinds of formulations surveyed
Examination.2 Specialized nursings are assigned to carry out whole observation, the physical condition of the tested volunteer of interview in each car.The result of table 2 is shown
The dexchlorpheniramine of various formulations and dosage has relatively good preventive effect, wherein dexchlorpheniramine 2.5mg to carsickness
Oral liquid and 1.25mg mouth sprays all substantially than corresponding dosage raceme chlorphenamine have stronger prevention cinetosis
Disease curative effect, and there is preferably prevention cinetosis than hyoscine (0.2mg) group and diphenhydramine (50mg) group of positive control
Disease acts on.The prevention motion sickness effect of dexchlorpheniramine 1.25mg oral liquid formulation and raceme chlorphenamine 10mg agent
The therapeutic equivalence of amount.The effect of two spray-type 1.25mg (spray I) and 2.5mg (spray II) pre- carsickness-proof is than corresponding
The preventive effect of the oral liquid formulation of dosage is good.
Embodiment 6
4 extra large ferryboaies are have selected, 486 volunteers for having carsick history has been randomly choosed and has participated in test.Volunteer tester
Intake in 30 minutes (oral, mucous membrane of mouth, transdermal patch) test medicine, drugs compared or blank (50% G/W before going on board
Solution), about 4 hours of marine stroke.In order to obtain more accurately data, by volunteer according to test medicine, right
It is marked according to medicine or blank product, each test article is equipped with 4 Specialized nursings and carries out whole record and interview.Wherein, it is right
Revolve chlorphenamine 4 kinds of oral liquid formulations of maleate (1.25 mg, 2.5mg, 5mg, 10mg), 2 kinds of mouthspray formulation (sprays
I：1.25mg/ sprays), spray II：2.5mg/ sprays), 2 kinds of Transdermal patch dosage forms (patch I：5mg/ is pasted, patch II：10 mg/ are pasted)；One
Plant hyoscine (" the phenobarbital Scopolamine Hydrobromide Tablets " of Guangzhou BaiYunshan GuangHua Pharmacy Co., Ltd's production：Every hydrogeneous
Bromic acid hyoscine 0.2mg)；A kind of diphenhydramine (" dimenhydrinate tablets " of Shanghai Jinshan pharmaceutical Co., Ltd.'s production：Every
Containing diphenhydramine 50mg)；A kind of blank control liquid (D/W 10mL), altogether 14 kinds of formulations be tested.Nursing
Personnel have carried out careful observation, interview to the tested volunteer of all 4 times seagoing vessels, the results are shown in Table 3.The result of table 3 shows various
Dexchlorpheniramine, raceme chlorphenamine, hyoscine, the diphenhydramine of formulation dosage have certain pre- preventive effect to seasick
Really.Wherein dexchlorpheniramine anti-motion sickness substantially it is better than the effect of corresponding raceme chlorphenamine, raceme chlorobenzene that
The anti-corona efficiency of oral liquid of quick 10mg dosage is suitable with the dexchlorpheniramine oral liquid effect of 1.25mg dosage.
According to the result of embodiment 5 and 6, testing drug all show some slight side effects, wherein dextrorotation chlorobenzene that
The uncomfortable reaction of quick test group is most slight, shows as drowsiness, dry, weak etc. (table 2, table 3).Racemization chlorphenamine test group
Discomfort reaction is similar with the same dose of dexchlorpheniramine, shows as drowsiness, dry, weak etc..The dextrorotation chlorine of same dose
That quick anti-motion sickness activity of benzene is higher than raceme chlorphenamine, but side effect is but not above raceme chlorphenamine, from
And reach that identical treatment effect needs the d-isomer chlorphenamine of lower dosage and generation less not with raceme chlorphenamine
Good reaction.The side effect of tested group of hyoscine and tested group of diphenhydramine apparently higher than tested group of all dexchlorpheniramines,
Also apparently higher than tested group of raceme chlorphenamine.The uncomfortable reaction of wherein hyoscine test group is drowsiness, dry, it is weak,
Impatient, constipation, and the discomfort reaction of diphenhydramine test group is drowsiness, dry, weak, headache.The uncomfortable reaction of blank control group
For drowsiness, dry, weak, dizzy, headache, Nausea and vomiting.Our result of the test shows dexchlorpheniramine as pre- anti-corona
Dynamic disease drug all has more preferable effect and relatively low side effect than racemization chlorphenamine, hyoscine and diphenhydramine.
Claims (9)
1. the preparation for treating, preventing or alleviating motion sickness, wherein the preparation contains the structural formula I of effective dose dextrorotation chlorine
That quick or its pharmaceutically acceptable salt of benzene
2. preparation according to claim 1, wherein the preparation only containing the dexchlorpheniramine of effective dose or its can pharmaceutically connect
The salt received is as active component.
3. according to the preparation of claim 1 or 2, wherein the preparation also contains pharmaceutical carrier or excipient.
4. according to the preparation of claim 1 or 2, wherein the pharmaceutically acceptable salt is selected from hydrochloride, sulfate, phosphoric acid
Salt, maleate, oxalates, citrate, tartrate, mesylate, tosilate, benzoate, acetate, it is excellent
Elect maleate as.
5. according to the preparation of claim 1 or 2, wherein the formulation of the preparation can be tablet, oral liquid, capsule, particle
Agent, parenteral solution, patch, paste, lozenge, lozenge, chewable tablets, the molten film of mouth, effervescent tablet, suspension, chewing gum, it is preferably oral
Liquid or chewing gum.
6. according to the preparation of claim 1 or 2, wherein the preparation also moves disease drug containing other anti-blooming, the medicine is selected from：
Hyoscine, diphenhydramine, Cyclizine, meclozine, fenazil, cinnarizine.
7. structural formula I dexchlorpheniramine or its salt are preparing the use in being used to treating, prevent or alleviating the preparation of motion sickness
On the way
8. purposes according to claim 8, the formulation of the preparation can be tablet, oral liquid, capsule, granule, note
Penetrate the molten film of liquid, patch, paste, lozenge, lozenge, chewable tablets, mouth, effervescent tablet, suspension, preferably chewing gum, oral liquid.
9. according to any one of claim 1-7 preparation and the purposes of claim 8 or 9, wherein the concentration of the oral liquid is
0.5-50mg/ml, preferably 1-20mg/ml, more preferably 1-10mg/ml, such as 1.25,2.5,5,10mg/ml, wherein patch use
Amount is 4mg-50mg/ patches, and preferably 4mg-10mg/ patches, the wherein consumption of spray are sprayed for 0.5mg-10mg/, preferably 1mg-
5mg/ sprays.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110772524A (en) * | 2019-12-11 | 2020-02-11 | 方科伟 | Pharmaceutical composition for treating motion sickness |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040225019A1 (en) * | 2003-02-25 | 2004-11-11 | Buckey Jay C. | Methods of preventing or treating motion sickness |
| CN101264080A (en) * | 2008-04-25 | 2008-09-17 | 北京阜康仁生物制药科技有限公司 | Pharmaceutical composition containing dexchlorpheniramine and preparation thereof |
-
2017
- 2017-07-25 CN CN201710611678.7A patent/CN107252426A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040225019A1 (en) * | 2003-02-25 | 2004-11-11 | Buckey Jay C. | Methods of preventing or treating motion sickness |
| CN101264080A (en) * | 2008-04-25 | 2008-09-17 | 北京阜康仁生物制药科技有限公司 | Pharmaceutical composition containing dexchlorpheniramine and preparation thereof |
Non-Patent Citations (3)
| Title |
|---|
| JAY C. BUCKEY等: "Chlorpheniramine for motion sickness", 《JOURNAL OF VESTIBULAR RESEARCH》 * |
| 刘宏民等: "《药物化学》", 31 August 2007, 第四军医大学出版社 * |
| 张世良等: "右旋氯苯那敏混悬液和医用凡士林缓解经鼻持续正压通气鼻部副作用的效果", 《中国医师进修杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110772524A (en) * | 2019-12-11 | 2020-02-11 | 方科伟 | Pharmaceutical composition for treating motion sickness |
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Application publication date: 20171017 |