CN111714509A - Application of dioscin in medicine for preventing and treating motion sickness - Google Patents
Application of dioscin in medicine for preventing and treating motion sickness Download PDFInfo
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- CN111714509A CN111714509A CN202010722916.3A CN202010722916A CN111714509A CN 111714509 A CN111714509 A CN 111714509A CN 202010722916 A CN202010722916 A CN 202010722916A CN 111714509 A CN111714509 A CN 111714509A
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- Prior art keywords
- dioscin
- preventing
- medicine
- motion sickness
- treating motion
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- HDXIQHTUNGFJIC-UHFFFAOYSA-N (25R)-spirost-5-en-3beta-ol 3-O-<O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside> Natural products O1C2(OCC(C)CC2)C(C)C(C2(CCC3C4(C)CC5)C)C1CC2C3CC=C4CC5OC1OC(CO)C(O)C(O)C1OC1OC(C)C(O)C(O)C1O HDXIQHTUNGFJIC-UHFFFAOYSA-N 0.000 title claims abstract description 100
- VNONINPVFQTJOC-RXEYMUOJSA-N Collettiside III Natural products O([C@@H]1[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@H](O)[C@@H](O)[C@H](C)O2)[C@H](CO)O[C@@H]1O[C@@H]1CC=2[C@@](C)([C@@H]3[C@H]([C@H]4[C@@](C)([C@H]5[C@H](C)[C@@]6(O[C@H]5C4)OC[C@H](C)CC6)CC3)CC=2)CC1)[C@H]1[C@H](O)[C@H](O)[C@@H](O)[C@H](C)O1 VNONINPVFQTJOC-RXEYMUOJSA-N 0.000 title claims abstract description 100
- VNONINPVFQTJOC-ZGXDEBHDSA-N dioscin Chemical compound O([C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)O[C@H]1[C@@H]([C@H](O)[C@@H](O)[C@H](C)O1)O)O[C@@H]1CC2=CC[C@H]3[C@@H]4C[C@H]5[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@@H]([C@]1(OC[C@H](C)CC1)O5)C)[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O VNONINPVFQTJOC-ZGXDEBHDSA-N 0.000 title claims abstract description 100
- CJNUQCDDINHHHD-APRUHSSNSA-N dioscin Natural products C[C@@H]1CC[C@@]2(OC1)O[C@H]3C[C@H]4[C@@H]5CC=C6C[C@H](CC[C@@H]6[C@H]5CC[C@]4(C)[C@H]3[C@@H]2C)O[C@@H]7O[C@H](CO)[C@@H](O[C@@H]8O[C@@H](C)[C@H](O)[C@@H](O)[C@H]8O)[C@H](O)[C@H]7O[C@@H]9O[C@@H](C)[C@H](O)[C@@H](O)[C@H]9O CJNUQCDDINHHHD-APRUHSSNSA-N 0.000 title claims abstract description 100
- VNONINPVFQTJOC-UHFFFAOYSA-N polyphyllin III Natural products O1C2(OCC(C)CC2)C(C)C(C2(CCC3C4(C)CC5)C)C1CC2C3CC=C4CC5OC(C(C1O)OC2C(C(O)C(O)C(C)O2)O)OC(CO)C1OC1OC(C)C(O)C(O)C1O VNONINPVFQTJOC-UHFFFAOYSA-N 0.000 title claims abstract description 100
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- 239000003826 tablet Substances 0.000 claims abstract description 21
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- 239000000049 pigment Substances 0.000 claims abstract description 4
- 239000006187 pill Substances 0.000 claims abstract description 4
- 239000000829 suppository Substances 0.000 claims abstract description 4
- 239000007939 sustained release tablet Substances 0.000 claims abstract description 4
- 239000002674 ointment Substances 0.000 claims abstract description 3
- 229940079593 drug Drugs 0.000 claims description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 6
- 238000010253 intravenous injection Methods 0.000 claims description 4
- BSYNFGPFPYSTTM-UHFFFAOYSA-N 2-hydroxypropanoic acid;hydrate Chemical compound O.CC(O)C(O)=O BSYNFGPFPYSTTM-UHFFFAOYSA-N 0.000 claims description 3
- 108010010803 Gelatin Proteins 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 229930006000 Sucrose Natural products 0.000 claims description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 3
- 239000004327 boric acid Substances 0.000 claims description 3
- 229920000159 gelatin Polymers 0.000 claims description 3
- 239000008273 gelatin Substances 0.000 claims description 3
- 235000019322 gelatine Nutrition 0.000 claims description 3
- 235000011852 gelatine desserts Nutrition 0.000 claims description 3
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 claims description 3
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- 239000008101 lactose Substances 0.000 claims description 3
- 239000000314 lubricant Substances 0.000 claims description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 3
- 238000010254 subcutaneous injection Methods 0.000 claims description 3
- 239000007929 subcutaneous injection Substances 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- 239000000080 wetting agent Substances 0.000 claims description 3
- 239000008297 liquid dosage form Substances 0.000 claims description 2
- 239000007909 solid dosage form Substances 0.000 claims description 2
- 241000700159 Rattus Species 0.000 description 37
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- 229940081974 saccharin Drugs 0.000 description 18
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 18
- 235000019204 saccharin Nutrition 0.000 description 18
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 18
- 230000008673 vomiting Effects 0.000 description 15
- 230000000694 effects Effects 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 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 11
- 238000009472 formulation Methods 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 206010047700 Vomiting Diseases 0.000 description 9
- 230000035622 drinking Effects 0.000 description 9
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- 230000009467 reduction Effects 0.000 description 8
- 210000004916 vomit Anatomy 0.000 description 8
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- 238000013461 design Methods 0.000 description 3
- 229960004993 dimenhydrinate Drugs 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 235000005903 Dioscorea Nutrition 0.000 description 2
- 244000281702 Dioscorea villosa Species 0.000 description 2
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- 206010024264 Lethargy Diseases 0.000 description 2
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- 206010047513 Vision blurred Diseases 0.000 description 2
- 208000022531 anorexia Diseases 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000001143 conditioned effect Effects 0.000 description 2
- 206010061428 decreased appetite Diseases 0.000 description 2
- 235000004879 dioscorea Nutrition 0.000 description 2
- 206010013781 dry mouth Diseases 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
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- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 241000305491 Gastrodia elata Species 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 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 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 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 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- 240000008154 Piper betle Species 0.000 description 1
- 235000008180 Piper betle Nutrition 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- 241000304195 Salvia miltiorrhiza Species 0.000 description 1
- 235000011135 Salvia miltiorrhiza Nutrition 0.000 description 1
- 208000008630 Sialorrhea Diseases 0.000 description 1
- 208000032140 Sleepiness Diseases 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 239000000150 Sympathomimetic Substances 0.000 description 1
- 244000273928 Zingiber officinale Species 0.000 description 1
- 235000006886 Zingiber officinale Nutrition 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
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- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 229940124623 antihistamine drug Drugs 0.000 description 1
- -1 antihistamine drugs Substances 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
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- 230000020595 eating behavior Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000030135 gastric motility Effects 0.000 description 1
- 235000008397 ginger Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 235000021056 liquid food Nutrition 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000008897 memory decline Effects 0.000 description 1
- 208000020470 nervous system symptom Diseases 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 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 description 1
- 229960002646 scopolamine Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
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- 239000011780 sodium chloride Substances 0.000 description 1
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- 235000021055 solid food Nutrition 0.000 description 1
- 201000008210 space motion sickness Diseases 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000003239 susceptibility assay Methods 0.000 description 1
- 229940127230 sympathomimetic drug Drugs 0.000 description 1
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- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- GYHCTFXIZSNGJT-UHFFFAOYSA-N tolvaptan Chemical compound CC1=CC=CC=C1C(=O)NC(C=C1C)=CC=C1C(=O)N1C2=CC=C(Cl)C=C2C(O)CCC1 GYHCTFXIZSNGJT-UHFFFAOYSA-N 0.000 description 1
- 229960001256 tolvaptan Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
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- 229940126680 traditional chinese medicines Drugs 0.000 description 1
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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
Abstract
The invention discloses an application of dioscin in a medicine for preventing and treating motion sickness, and relates to the technical field of application of dioscin; the medicine of dioscin for preventing and treating motion sickness is prepared by mixing pharmaceutically acceptable carrier and dioscin to prepare medicine of specific dosage form; the specific dosage form comprises tablet, capsule, pill, suppository, unguent, liquid, emulsion, and granule. The tablet comprises one of common tablet, enteric-coated tablet, dispersible tablet, quick-release tablet, sustained-release tablet, and controlled-release tablet; the pharmaceutically acceptable carrier of dioscin also comprises one or more of pH buffer, emulsifier, pigment and dye, and the dioscin can play an effective reference role in preventing and treating motion sickness, and further play an effective pharmaceutical role.
Description
Technical Field
The invention belongs to the application field of dioscin, and particularly relates to application of dioscin in a medicine for preventing and treating motion sickness.
Background
Motion sickness, also known as motion sickness, is a syndrome of vegetative nervous system symptoms such as lethargy, headache, pale complexion, stomach discomfort, nausea and vomiting, which are caused by the body being in a motion environment or simulated motion environment. Motion sickness can be induced in a variety of motion environments, such as automobiles, boats, airplanes, pendulum trains, space, simulated motion. The motion sickness is classified into car sickness, sea sickness, simulator motion sickness, aviation motion sickness, space motion sickness and the like according to different motion sickness environments.
The existing anti-motion sickness drugs comprise anticholinergic drugs, antihistamine drugs, sympathomimetic drugs, calcium antagonist, gastric motility drugs, and also traditional Chinese medicines such as salvia miltiorrhiza, gastrodia elata, ginger and the like. The single drug with the best effect of preventing and treating the motion sickness is scopolamine, and the most common drug is antihistaminic drug, namely dimenhydrinate (theohydramine tablets).
The inventor of the application finds that the common anti-motion sickness drugs have large side effects in the long-term research and development process, can cause sleepiness, blurred vision, dry mouth, reduction of gastrointestinal and respiratory tract secretions, difficulty in concentration of attention, memory reduction and the like, and can influence the operation of people under various special environmental conditions.
Disclosure of Invention
The technical problem to be solved is as follows: aiming at the technical problems that the common anti-motion sickness drugs have large side effects and can cause lethargy, blurred vision, dry mouth, reduction of gastrointestinal and respiratory tract secretions, difficulty in concentrating attention, memory decline and the like, the invention aims to provide the application of dioscin in the drugs for preventing and treating the motion sickness.
The technical scheme is as follows:
an application of dioscin in medicine for preventing and treating motion sickness is disclosed, wherein the chemical structural formula of dioscin is shown in the specification
Further, the medicine for preventing and treating motion sickness comprises a pharmaceutically acceptable carrier of dioscin.
Furthermore, the medicine of the dioscin for preventing and treating the motion sickness is prepared by mixing a pharmaceutically acceptable carrier with the dioscin to prepare a medicine forming a specific dosage form.
Further, the specific dosage forms include tablets, capsules, pills, suppositories, ointments, liquids, emulsions, and granules.
Further, the dioscin can be used for preventing and treating motion sickness by selecting drugs with corresponding dosage forms according to oral administration or non-oral administration, and one or more of the administration routes can be used by the same patient, and the non-oral administration route can be intravenous injection, intramuscular injection and subcutaneous injection.
Further, the tablet comprises one of common tablets, enteric-coated tablets, dispersible tablets, quick-release tablets, sustained-release tablets and controlled-release tablets.
Further, when the dosage form is a solid dosage form, the pharmaceutically acceptable carrier of the dioscin comprises: the excipient is lactose and/or sucrose, the binder is one or more of water, ethanol, propanol and gelatin solution, the wetting agent is glycerol, and the lubricant is one or more of stearate, boric acid powder and polyethylene glycol.
Further, when the dosage form is a liquid dosage form, the pharmaceutically acceptable carrier of the dioscin is a diluent, and the diluent is one or more of water, ethanol, propylene glycol and lactic acid water solution.
Further, the pharmaceutically acceptable carrier of the dioscin also comprises one or more of pH buffer, emulsifier, pigment and dye.
Furthermore, the medicines for treating motion sickness are in dosage unit form, the dosages of the dioscin contained in the medicines with different dosage forms can be the same or different, and the dosages of the dioscin contained in the medicines with the same dosage form can be the same or different; for example, the dosage of dioscin contained in the drug, which is also in a liquid form, may be 30mg or 60 mg.
Has the advantages that:
1. the medicine for preventing and treating motion sickness comprises dioscin with effective dose for preventing and treating motion sickness and a pharmaceutically acceptable carrier. Wherein, the dioscin can play an effective reference role in preventing and treating motion sickness, and further possibly play an effective medicine role.
2. The vomit latency of beagle dog in high dosage of dioscin is 21.93 + -3.53 min, which is significantly prolonged compared with 10.36 + -3.04 min in control group and 10.91 + -3.17 min in low dosage of dioscin. With the increase of dosage of dioscin, the vomit latency of beagle dogs after rotary stimulation is gradually increased, and the beagle dogs can play the same role as dimenhydrinate, wherein the difference between the high-dosage group of dioscin and the control group is obvious (p is less than 0.05).
3. After the rotation stimulation, the percentage of the decrease of the saccharin drinking water consumption of rats in the rotation stimulation group is 33.13 +/-4.75, and is obviously reduced compared with the rats in the normal saline group (p is less than 0.01), while the percentage of the decrease of the saccharin drinking water consumption of rats in the dioscin high dose group is 17.23 +/-3.64, and is obviously increased relative to the rotation stimulation group, and the difference has significance (p is less than 0.05), and the effect is similar to the result of a theohydramine positive drug control group.
Detailed Description
The following examples illustrate specific steps of the present invention, but are not intended to limit the invention.
Terms used in the present invention generally have meanings commonly understood by those of ordinary skill in the art, unless otherwise specified.
The invention is described in further detail below with reference to specific examples and with reference to data. It will be understood that these examples are intended to illustrate the invention and are not intended to limit the scope of the invention in any way.
In the following examples, various procedures and methods not described in detail are conventional methods well known in the art.
The rotary stimulation device was modeled with reference to Crampton and Lucot reports. Crampton GH, Lucot JB, analyzer for laboratory students of motion in cats, Aviat SpaceEnviron Med.,1985.56(5): 462-.
Example 1
An application of dioscin in medicine for preventing and treating motion sickness is disclosed, wherein the chemical structural formula of dioscin is shown in the specification
The medicine for preventing and treating motion sickness comprises a pharmaceutically acceptable carrier of dioscin, the medicine for preventing and treating motion sickness of dioscin is a medicine prepared by mixing the pharmaceutically acceptable carrier and the dioscin to form a specific dosage form, the specific dosage form comprises a tablet, a capsule, a pill, a suppository, a paste, a liquid, an emulsion and a granule, the medicine for preventing and treating motion sickness of dioscin selects the corresponding dosage form according to the oral administration or non-oral administration route, one or more of the administration routes can be used by the same patient, the non-oral administration route comprises intravenous injection, intramuscular injection and subcutaneous injection, and the tablet comprises one of a common tablet, an enteric coated tablet, a dispersible tablet, a quick release tablet, a sustained release tablet and a controlled release tablet; the pharmaceutically acceptable carrier of dioscin also comprises one or more of pH buffer, emulsifier, pigment, and dye.
When the dosage form is solid, the pharmaceutically acceptable carrier of dioscin comprises: the excipient is lactose and/or sucrose, the binder is one or more of water, ethanol, propanol and gelatin solution, the wetting agent is glycerol, and the lubricant is one or more of stearate, boric acid powder and polyethylene glycol; when the dosage form is liquid, the pharmaceutically acceptable carrier of dioscin is diluent, wherein the diluent is one or more of water, ethanol, propylene glycol, and lactic acid water solution; the medicine for preventing and treating motion sickness is in dosage unit form, the dosage of dioscin contained in the medicine with different dosage forms can be the same or different, and the dosage of dioscin contained in the medicine with the same dosage form can be the same or different; for example, the dosage of dioscin contained in the drug, which is also in a liquid form, may be 30mg or 60 mg.
In one application scenario, the skilled physician can readily determine and prescribe the effective amount of dioscin in a drug for the treatment of a disease, depending on the species of the patient (e.g., dog, chimpanzee, etc.), sex, weight, age, medical condition, route of administration, severity of the condition being treated, and the like. In addition, the effective dose administered will vary with the mode of administration, the treatment desired, and the disease condition indicated. The total daily dose may be administered in a single dose or in divided doses. For example, in the case of a single intravenous injection of a medicine for preventing and treating motion sickness in an adult, the dosage of dioscin in the medicine is 30-60mg, for example, 30mg, 40mg, 50mg, 60 mg.
The above listed dosage ranges are exemplary only, and dosages may be adjusted according to pharmacokinetic or pharmacodynamic parameters, which may include clinical effects such as toxic effects and/or laboratory values. Accordingly, this application encompasses dose escalation in patients as determined by one of skill in the art. Determining appropriate dosages and regimens for administering dioscin is well known in the relevant art, and should be understood to be covered by those skilled in the art once provided with the teachings disclosed herein.
The medicaments of the present application may be prepared, packaged or sold in bulk form, in single unit dosage form, or in multiple single unit dosage forms. As used herein, a "unit dose" is an individual amount of a drug that contains a predetermined amount of dioscin. The amount of dioscin is generally equal to the dose of dioscin to be administered to the subject, or a convenient fraction of such a dose, e.g., one-half or one-third of such a dose.
The relative amounts of dioscin, a pharmaceutically acceptable carrier, and any other ingredients in the medicaments of the present application will vary depending on the identity, size, and condition of the subject being treated, and further depending on the route of administration of the composition. For example, the composition may comprise between 0.1% and 100% (w/w) dioscin.
The agent for preventing and treating motion sickness in the present application may further comprise one or more other agents effective for preventing and treating motion sickness, the components of which are in the same formulation or separate formulations for simultaneous administration or sequential administration.
In an application scenario, the medicine for preventing and treating motion sickness comprises at least two active components, namely a first active component and a second active component, wherein the first active component is dioscin; the first active ingredient and the carrier are used in a conventional formulation process to form a first formulation, the second active ingredient and the carrier are used in a conventional formulation process to form a second formulation, and the patient sequentially injects the first formulation and the second formulation. In another application scenario, the first active ingredient, the second active ingredient, and the carrier are used in a conventional formulation process to form a third formulation, which is injected by the patient. In still another application scenario, the effective dosage ratio of the first active component and the second active component is 1:1, 2:1, 1:2, etc., and the effective dosage ratio can be adjusted by the physician according to the actual situation.
The following data are presented to show that dioscin provides an effective reference for preventing and treating motion sickness.
Experimental materials:
the experimental animal beagle dog is 20 beagle dog, each half male and female, the weight is 7.5-10.5kg, the beagle dog is purchased from Shanghai university of transportation experimental animal farm, healthy Sprague-Dawley rat, clean grade, 60 beagle dogs, each half male and female, the weight is 220 plus 260g, and the beagle dog is provided by Nantong university medical experimental animal center.
The experimental method comprises the following steps:
1. rat and beagle motion disease model preparation: during the experiment, rats or dogs are placed in the organic glass cage of the rotating device without being bound and rotate around the horizontal shaft. Clockwise acceleration and deceleration and anticlockwise acceleration and deceleration are carried out alternately, the acceleration time is 7.5s, and the deceleration time is 2.5s, namely 20s in one period. The acceleration at acceleration is 16 DEG/s2Acceleration at deceleration of-48 DEG/s2Rotation amplitude 700 deg., time 10 s. The rat rotation was stopped for 120min and the dog rotation for 30 min.
2. Determination of the sensitivity of beagle motion disease: the dogs are numbered 16 beagle dogs, are bred adaptively for 1 week, are given rotary stimulation for 30min, record the occurrence time (in min) of the sialorrhea and the vomiting of the dogs, and stop rotating if the dogs rotate for 30min, and are marked as insensitive to motion diseases. Beagle dogs were screened twice with 2 weeks interval. And (3) combining the experimental data of two times, grouping 16 beagle dogs into motion disease sensitivity groups according to the existence of vomit symptoms, selecting 16 sensitive groups and 4 insensitive groups, and selecting 10 sensitive groups for drug tests.
3. Beagle drug test design: the beagle drug test adopts the Latin prescription design, 2 dogs in each group are subjected to the drug test every 1 week, and the test is divided into: a normal saline control group (given equal volume of normal saline), a positive control drug of thehydramine group of 0.3125mg/kg vomit latency of 24.58 +/-3.04 min; dioscin low dose group: 0.125mg/kg body weight; the dosage group of dioscin is as follows: 0.25mg/kg body weight; dioscin high dose group: 0.5mg/kg body weight. The corresponding drugs of the beagle dogs are respectively given orally before the rotary stimulation, the rotary stimulation is carried out after 60min, and the vomit occurrence time is recorded.
4. Rat motion disease susceptibility assay: animal motion disease models for experimental study include models for directly producing emesis by abnormal stimulation, and animals to be studied include dogs, cats, monkeys, etc.; there are two models of changes in eating behavior that result from rotational stimulation, including pica and conditioned anorexia (CTA). Animals used in the pica model include white rats, guinea pigs, etc., and when stimulated, the animals develop motion sickness, and more kaolin is ingested by the animals. The CTA model uses many animals, including rats and monkeys, cats, guinea pigs, rats, quails, mice, etc., and the animals show a decrease in the intake of a certain liquid or solid food with a certain color, odor, or taste, due to the onset of motion sickness caused by the rotational stimulation.
The rats are judged and grouped according to the conditioned anorexia: 60 rats are numbered and randomly divided into 4 groups, and the groups are respectively placed in an experimental animal box to freely ingest water and seek food and are adaptively raised for 3-4 days. And (3) screening the water is cut off for 24h on the first day, the saccharin water with the concentration of 0.15% is freely drunk for 45min on the second day, recording the water consumption amount of the saccharin, freely drinking the water, giving a rotary stimulus for 120min on the third day, cutting off the water for 24h, freely drinking the saccharin water with the concentration of 0.15% for 45min on the fourth day, and recording the water consumption amount of the saccharin. The rats in the same batch are rested for 2 weeks, normal drinking water is recovered, the experiment is repeated for 1 time, the percentage of reduction of the saccharin drinking water consumption after the rats are rotationally stimulated is calculated, and the average experiment result of 2 times is that 4 groups of rats are respectively divided into a sensitive group and an insensitive group, namely, the rats with the saccharin drinking water consumption reduction percentage more than or equal to 15% are the sensitive group, and the rats with the saccharin drinking water consumption reduction percentage less than or equal to 15% are the insensitive group. 48 sensitive rats were screened, 12 insensitive rats were screened, and 48 sensitive rats were tested for drugs.
5. Rat drug test design: the rats were randomly divided into 4 groups of 12 rats each, which were: normal saline control group, rotary stimulation group, dioscin high dose (1.8mg/kg) group, and positive control drug Theophediamine (1.125 mg/kg). The first day in the morning 0.15% saccharin sodium solution was dosed for 24h, with normal drinking tap water. The following day morning, 0.15% saccharin water was continued, the third day morning, 0.15% saccharin water was continued and the 0.15% saccharin water consumption was recorded for each group of SD rats. Injecting appropriate amount of reagents prepared according to body weight into abdominal cavity with 1mL syringe in the morning on the fourth day, wherein the normal saline control group, the rotary stimulation group, the dioscin high dose group and the positive control medicine of dimenhydrinate group are respectively as follows: 1ml/200g normal saline, 0.36mg/200g dioscin, 0.225mg/200g tolvaptan, rotating and stimulating the rats in the rotating and stimulating group, the dioscin high dose group and the positive control drug theohydramine group for 120min after 30 min. The administration of 0.15% aqueous saccharin was then continued, and the drinking of aqueous saccharin was continued for each two-day group of SD rats on the fifth and sixth morning days. Calculating the average daily drinking amount of each group of rats according to the drinking amounts of the saccharin aqueous solution in two days before and two days after the rotary stimulation, calculating the percentage of reduction of the drinking amount of the saccharin aqueous solution of each group of rats after the rotary stimulation, and judging the conditioned taste aversion degree of the rats induced by the rotary stimulation and the influence of the dioscin.
Results of the experiment
TABLE 1 Effect of drugs on the vomiting latency of beagle dogs (
n＝12)
| Group of | Incubation period for vomiting (min) |
| Physiological saline group | 10.36±3.04 |
| Dimenhydrinate group | 23.85±2.84* |
| Dioscorea saponin low dose group | 10.91±3.17 |
| Dioscorea saponin middle dose group | 12.01±2.89 |
| High dosage group of dioscin | 21.93±3.53*# |
Note: p <0.05, compared to control group; # p <0.05, compared to the low dose group
The results in Table 1 show that the vomit latency of the betel dogs in the dioscin medium dose group is increased compared with that in the normal saline group. The vomit incubation period of the beagle dog in the dioscin high-dose group is obviously prolonged compared with that of the control group and the dioscin low-dose group. With the increase of dosage of dioscin, the vomit latency of beagle dogs after rotary stimulation is gradually increased, and the beagle dogs can play the same role as dimenhydrinate, wherein the difference between the high-dosage group of dioscin and the control group is obvious (p is less than 0.05). This indicates that the high dose group of dioscin can prolong the incubation period of vomiting after rotary stimulation of beagle dogs, i.e., dioscin has anti-motion sickness effect.
TABLE 2 Effect of drugs on conditioned taste aversion in Rotatary stimulation induced rats: (
n＝10)
| Group of | Percentage reduction of saccharin sodium solution |
| Physiological saline group | 9.50±3.86 |
| Rotary stimulation group | 33.13±4.75* |
| Dimenhydrinate group | 15.82±2.19* |
| High dosage group of dioscin | 17.23±3.64# |
Note: p <0.01 compared to saline group; # and P <0.05, compared to the rotary stimulation group.
The results in table 2 show that after the rotation stimulation, compared with the normal saline group rats, the saccharin drinking amount of the rotation stimulation group rats is obviously reduced (p is less than 0.01), while the saccharin drinking amount of the dioscin high-dose group rats is obviously increased relative to the rotation stimulation group, and the difference has significance (p is less than 0.05), and the effect is similar to the result of the theohydramine positive drug control group. This indicates that the dioscin high dose group can significantly inhibit conditioned taste aversion of SD rats induced by rotational stimulation, and the effect is comparable to that of the positive control drug theohydramine.
The application carries out the relevant rotary stimulation experimental research on the aspect of preventing and treating the motion sickness by the dioscin, proves that the dioscin has definite effect of preventing and treating the motion sickness, and provides a more complete experimental basis for the dioscin serving as a novel medicine for preventing and treating the motion sickness and the clinical application thereof. Different drug types and dosage groups are designed by taking beagles and SD rats as research objects to carry out a rotation stimulation experiment, which proves that the dioscin can prevent and treat the motion disease. The results show that the dioscin can prolong the vomiting latency period induced by the beagle rotational stimulation and can inhibit conditioned taste aversion induced by the SD rat rotational stimulation. In addition, in two aspects of prolonging the vomiting latency after the beagle dog is subjected to rotational stimulation and inhibiting the conditioned taste aversion induced by the SD rat, the effect of prolonging the vomiting latency or inhibiting the conditioned taste aversion is more obvious along with the increase of the dosage of the dioscin, which shows that the dosage of the dioscin has certain influence on the curative effect. The dioscin is developed into a medicine for preventing and treating motion sickness, has good application prospect, and has important significance in promoting human health and promoting the development of transportation industry such as aviation, aerospace, navigation and the like in China.
Claims (10)
1. The application of dioscin in the medicine for preventing and treating motion sickness is characterized in that: the chemical structural formula of the dioscin is shown as
2. The use of dioscin as a medicine for preventing and treating motion sickness according to claim 1, wherein: the medicine for preventing and treating motion sickness comprises a pharmaceutically acceptable carrier of dioscin.
3. The use of dioscin as a medicine for preventing and treating motion sickness according to claim 2, wherein: the medicine of dioscin for preventing and treating motion sickness is prepared by mixing pharmaceutically acceptable carrier and dioscin to prepare medicine of specific dosage form.
4. The use of dioscin as a medicine for preventing and treating motion sickness according to claim 3, wherein: the specific dosage forms comprise tablets, capsules, pills, suppositories, ointments, liquids, emulsions and granules.
5. The use of dioscin as a medicine for preventing and treating motion sickness according to claim 4, wherein: the dioscin is used for preventing and treating motion sickness, and the medicines with corresponding dosage forms are selected according to the oral administration route or the non-oral administration route, wherein one or more of the administration routes can be used by the same patient, and the non-oral administration route is intravenous injection, intramuscular injection and subcutaneous injection.
6. The use of dioscin as a medicine for preventing and treating motion sickness according to claim 4, wherein: the tablet comprises one of common tablet, enteric-coated tablet, dispersible tablet, quick-release tablet, sustained-release tablet and controlled-release tablet.
7. The use of dioscin as a medicine for preventing and treating motion sickness according to claim 3, wherein: when the dosage form is a solid dosage form, the pharmaceutically acceptable carrier of the dioscin comprises: the excipient is lactose and/or sucrose, the binder is one or more of water, ethanol, propanol and gelatin solution, the wetting agent is glycerol, and the lubricant is one or more of stearate, boric acid powder and polyethylene glycol.
8. The use of dioscin as a medicine for preventing and treating motion sickness according to claim 3, wherein: when the dosage form is a liquid dosage form, the pharmaceutically acceptable carrier of dioscin is diluent, and the diluent is one or more of water, ethanol, propylene glycol and lactic acid water solution.
9. The use of dioscin as a medicine for preventing and treating motion sickness according to claim 3, wherein: the pharmaceutically acceptable carrier of dioscin also comprises one or more of pH buffer, emulsifier, pigment, and dye.
10. The use of dioscin as a medicine for preventing and treating motion sickness according to claim 3, wherein: the medicine for preventing and treating motion sickness is in dosage unit form, the dosage of the dioscin contained in the medicines with different dosage forms can be the same or different, and the dosage of the dioscin contained in the medicines with the same dosage form can be the same or different; for example, the dosage of dioscin contained in the drug, which is also in a liquid form, may be 30mg or 60 mg.
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| CN1586493A (en) * | 2004-07-05 | 2005-03-02 | 北京科信必成医药科技发展有限公司 | Dioscin oral disintegration tablet and its preparing method |
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