CN112791120A - Oral emulsion and its prepn and use - Google Patents
Oral emulsion and its prepn and use Download PDFInfo
- Publication number
- CN112791120A CN112791120A CN201911022519.9A CN201911022519A CN112791120A CN 112791120 A CN112791120 A CN 112791120A CN 201911022519 A CN201911022519 A CN 201911022519A CN 112791120 A CN112791120 A CN 112791120A
- Authority
- CN
- China
- Prior art keywords
- oral emulsion
- emulsifier
- emulsion
- oil
- pharmaceutical
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000839 emulsion Substances 0.000 title claims abstract description 102
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 55
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 claims abstract description 40
- GRWFGVWFFZKLTI-UHFFFAOYSA-N α-pinene Chemical compound CC1=CCC2C(C)(C)C1C2 GRWFGVWFFZKLTI-UHFFFAOYSA-N 0.000 claims abstract description 40
- 239000003814 drug Substances 0.000 claims abstract description 33
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims abstract description 30
- 229920000053 polysorbate 80 Polymers 0.000 claims abstract description 30
- WEEGYLXZBRQIMU-UHFFFAOYSA-N 1,8-cineole Natural products C1CC2CCC1(C)OC2(C)C WEEGYLXZBRQIMU-UHFFFAOYSA-N 0.000 claims abstract description 20
- GRWFGVWFFZKLTI-IUCAKERBSA-N 1S,5S-(-)-alpha-Pinene Natural products CC1=CC[C@@H]2C(C)(C)[C@H]1C2 GRWFGVWFFZKLTI-IUCAKERBSA-N 0.000 claims abstract description 20
- MVNCAPSFBDBCGF-UHFFFAOYSA-N alpha-pinene Natural products CC1=CCC23C1CC2C3(C)C MVNCAPSFBDBCGF-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229960005233 cineole Drugs 0.000 claims abstract description 20
- 239000007957 coemulsifier Substances 0.000 claims abstract description 20
- 229940087305 limonene Drugs 0.000 claims abstract description 20
- 235000001510 limonene Nutrition 0.000 claims abstract description 20
- WEEGYLXZBRQIMU-WAAGHKOSSA-N Eucalyptol Chemical compound C1C[C@H]2CC[C@]1(C)OC2(C)C WEEGYLXZBRQIMU-WAAGHKOSSA-N 0.000 claims abstract description 19
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims abstract description 18
- -1 polyoxyethylene Polymers 0.000 claims abstract description 14
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims abstract description 7
- 229920001213 Polysorbate 20 Polymers 0.000 claims abstract description 7
- 239000004359 castor oil Substances 0.000 claims abstract description 7
- 235000019438 castor oil Nutrition 0.000 claims abstract description 7
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims abstract description 7
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims abstract description 7
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims abstract description 7
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229920001993 poloxamer 188 Polymers 0.000 claims abstract description 4
- 229940044519 poloxamer 188 Drugs 0.000 claims abstract description 4
- 239000003921 oil Substances 0.000 claims description 56
- 235000019198 oils Nutrition 0.000 claims description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 48
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 46
- 229960004063 propylene glycol Drugs 0.000 claims description 20
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 12
- 235000012424 soybean oil Nutrition 0.000 claims description 12
- 239000003549 soybean oil Substances 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 239000004519 grease Substances 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 206010011224 Cough Diseases 0.000 claims description 4
- 206010062717 Increased upper airway secretion Diseases 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 208000026435 phlegm Diseases 0.000 claims description 4
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 claims description 3
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 claims description 3
- 229940093471 ethyl oleate Drugs 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 229960005150 glycerol Drugs 0.000 claims description 2
- 229940057917 medium chain triglycerides Drugs 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 229940068918 polyethylene glycol 400 Drugs 0.000 claims description 2
- 230000008030 elimination Effects 0.000 claims 1
- 238000003379 elimination reaction Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000001629 suppression Effects 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 17
- 238000000034 method Methods 0.000 abstract description 8
- 238000010521 absorption reaction Methods 0.000 abstract description 4
- 206010070840 Gastrointestinal tract irritation Diseases 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract 1
- 230000001737 promoting effect Effects 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 28
- 238000002360 preparation method Methods 0.000 description 17
- 230000001804 emulsifying effect Effects 0.000 description 15
- 238000010008 shearing Methods 0.000 description 11
- 239000002994 raw material Substances 0.000 description 10
- 238000005303 weighing Methods 0.000 description 10
- 238000005119 centrifugation Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 239000008213 purified water Substances 0.000 description 9
- 230000000954 anitussive effect Effects 0.000 description 7
- 230000003110 anti-inflammatory effect Effects 0.000 description 7
- 229940124584 antitussives Drugs 0.000 description 7
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 7
- 238000004945 emulsification Methods 0.000 description 7
- 230000003419 expectorant effect Effects 0.000 description 7
- 239000002131 composite material Substances 0.000 description 6
- 230000007794 irritation Effects 0.000 description 5
- 239000002245 particle Substances 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 238000009210 therapy by ultrasound Methods 0.000 description 4
- 239000000341 volatile oil Substances 0.000 description 4
- 235000005976 Citrus sinensis Nutrition 0.000 description 3
- 240000002319 Citrus sinensis Species 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 230000003467 diminishing effect Effects 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000007764 o/w emulsion Substances 0.000 description 3
- 239000008251 pharmaceutical emulsion Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 235000019202 steviosides Nutrition 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 2
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 2
- 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 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 2
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 239000004302 potassium sorbate Substances 0.000 description 2
- 235000010241 potassium sorbate Nutrition 0.000 description 2
- 229940069338 potassium sorbate Drugs 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical compound OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 229940013618 stevioside Drugs 0.000 description 2
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 125000002006 1,8-cineol group Chemical group 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 239000004383 Steviol glycoside Substances 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229930182488 steviol glycoside Natural products 0.000 description 1
- 235000019411 steviol glycoside Nutrition 0.000 description 1
- 150000008144 steviol glycosides Chemical class 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/61—Myrtaceae (Myrtle family), e.g. teatree or eucalyptus
-
- 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
- A61K31/01—Hydrocarbons
- A61K31/015—Hydrocarbons carbocyclic
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/10—Expectorants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a medicine oral emulsion, which comprises a medicine composition consisting of eucalyptol, limonene and alpha-pinene, an emulsifier and a co-emulsifier, wherein the emulsifier is selected from two or more of tween 80, tween 20, span 80, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil and poloxamer 188. The invention also provides a method for preparing the medicine oral emulsion and application of the medicine oral emulsion. The oral emulsion can reduce gastrointestinal irritation and improve patient compliance, and has small droplet size, good centrifugal stability and good drug absorption promoting effect.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to a pharmaceutical oral emulsion and a preparation method and application thereof. More specifically, the invention relates to a pharmaceutical oral emulsion containing eucalyptol, limonene and alpha-pinene, a preparation method and application thereof.
Background
The medicine composition of eucalyptol, limonene and alpha-pinene is a kind of cough relieving, inflammation diminishing and phlegm eliminating medicine with determined curative effect. At present, only enteric soft capsules are available for oral preparations containing eucalyptol, limonene and alpha-pinene, the problem of dysphagia is found in the market sale of children, and meanwhile, if the capsules are cracked and released in the stomach, pungent smell is reflected from the stomach, and the capsules also have certain irritation to the stomach. Meanwhile, the existing dosage form of the pharmaceutical composition has the problem of poor administration compliance of patients.
Therefore, there is a need to develop an oral formulation that reduces gastrointestinal irritation and improves patient compliance.
Disclosure of Invention
It is therefore an object of the present invention to provide a pharmaceutical oral emulsion that reduces gastrointestinal irritation and improves patient compliance. The medicinal oral emulsion has good centrifugal stability, the particle size of liquid drops can reach the nanometer level, and the medicinal absorption can be promoted.
Another object of the present invention is to provide a method for preparing the pharmaceutical oral emulsion of the present invention.
It is a further object of the present invention to provide a use of the pharmaceutical oral emulsion of the present invention.
In the present invention, the term "Emulsion" refers to a non-uniformly dispersed liquid preparation in which one phase is dispersed in a liquid of the other phase in a droplet state, wherein the two phases are immiscible with each other.
The purpose of the invention is realized by the following technical scheme.
In one aspect, the present invention provides a pharmaceutical oral emulsion comprising a pharmaceutical composition consisting of eucalyptol, limonene and alpha-pinene, and an emulsifier and a co-emulsifier, wherein the emulsifier is selected from two or more of tween 80, tween 20, span 80, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil and poloxamer 188.
The pharmaceutical oral emulsion provided by the invention is characterized in that the emulsifier is a tween 80 and span 80 compound emulsifier.
The medicine oral emulsion provided by the invention is characterized in that the content of the emulsifier is 3.0-6.0%, preferably 4.0-5.5% based on the weight of the medicine oral emulsion.
The pharmaceutical oral emulsion provided by the invention further comprises a co-emulsifier, wherein the co-emulsifier is selected from one or more of ethanol, propylene glycol, glycerol and polyethylene glycol, preferably one or more of propylene glycol, glycerol and polyethylene glycol 400, more preferably propylene glycol, and most preferably 1, 2-propylene glycol.
The pharmaceutical oral emulsion provided by the invention comprises 1.0-3.0% of the co-emulsifier, preferably 1.2-1.8% of the co-emulsifier based on the weight of the pharmaceutical oral emulsion.
The pharmaceutical oral emulsion provided by the invention further comprises oil and water; preferably, the oil or fat is selected from one or more of soybean oil, medium chain triglycerides and ethyl oleate, most preferably soybean oil.
The pharmaceutical oral emulsion provided by the invention comprises 5.0-20% of pharmaceutical composition by weight, preferably 5.0-13.0% of pharmaceutical composition by weight.
The medicine oral emulsion provided by the invention comprises 1.0-8.0% of oil and fat and 72.0-85.0% of water based on the weight of the medicine oral emulsion; preferably, the content of the grease is 3.0-5.0%, and the content of the water is 75.0-82.0%.
The pharmaceutical oral emulsion provided by the invention comprises 40.0-65.0% of eucalyptol, 20.0-45.0% of limonene and 5.0-25.0% of alpha-pinene based on the weight of the pharmaceutical composition.
According to the oral pharmaceutical emulsion provided by the invention, preferably, the emulsifier is two or more of tween 80, span 80, polyoxyethylene castor oil and poloxamer 188. Most preferably, the emulsifier is a mixture of span 80 and tween 80. In a most preferred embodiment, the weight ratio of span 80 to tween 80 is 1: 4-99.
In a preferred embodiment of the invention, the pharmaceutical oral emulsion is an oil-in-water emulsion.
In a preferred embodiment of the present invention, the pharmaceutical oral emulsion may further comprise flavoring agents, preservatives and/or stabilizers; preferably, the flavoring agent accounts for 0.5-3.0%, the preservative accounts for 0.1-1.2% and/or the stabilizer accounts for 0.05-0.15% of the weight of the oral pharmaceutical emulsion.
In certain embodiments of the invention, the flavoring agent is a sweetener and/or a fragrance; the preservative is selected from one or more of sodium benzoate, potassium sorbate, ethylparaben and sorbic acid; and/or the stabilizer is selected from hydroxymethyl cellulose and/or xanthan gum.
In certain embodiments of the invention, the sweetener is selected from one or more of steviol glycosides, sucrose, sodium saccharin, and aspartame; and/or the aromatic is selected from one or more of sweet orange essential oil, lemon essence, sweet orange essence and peppermint oil.
In another aspect, the present invention provides a method for preparing the pharmaceutical oral emulsion of the present invention, comprising the steps of:
(1) weighing the raw materials, adding eucalyptol, limonene and alpha-pinene into grease, and uniformly mixing to obtain medicated grease;
(2) adding emulsifier and co-emulsifier into the medicated oil, and mixing completely to form oil phase;
(3) directly using water as water phase or adding optional correctant, antiseptic and/or stabilizer into water, and mixing completely to form water phase;
(4) pouring the oil phase into the water phase, and mixing uniformly to obtain the medicinal oral emulsion.
In certain embodiments of the present invention, the mixing conditions in steps (1) to (3) of the preparation process comprise: stirring the mixture in a constant temperature water bath at 10-40 ℃, preferably 30 ℃, at a rotating speed of 30-60 r/min, preferably 45-55 r/min for 0.5-2 hours, preferably 1 hour. Preferably, in the step (4), the mixing is performed by an ultrasonic method, a milling method, a high-speed shearing method, and/or a homogenizing method.
In certain embodiments of the present invention, in step (4) of the preparation method, the pharmaceutical oral emulsion may be prepared by: shearing for 8-12 min (such as 10 min) at 8000-12000 r/min (such as 10000 r/min) with a high-speed shearing machine, and homogenizing for 2-5 min (such as 3 min) under 10-30 bar (such as 20 bar) pressure after shearing to obtain the oral emulsion.
In other embodiments of the present invention, in the step (4) of the preparation method, the pharmaceutical oral emulsion may be further prepared by: performing ultrasonic treatment in an ultrasonic instrument with frequency of 40-60 Hz, such as 50Hz, for 0.5-2 hours, such as 1 hour, to obtain primary emulsion, and then circulating in a homogenizer at 40-60 bar, such as 50bar, for 3-6 minutes, such as 5 minutes, to obtain the oral emulsion.
In a further aspect, the invention provides the use of a pharmaceutical oral emulsion according to the invention for the preparation of a medicament for relieving cough, diminishing inflammation and/or eliminating phlegm.
The types of emulsifiers and co-emulsifiers have a great influence on the emulsifying effect and the centrifugal stability of the prepared pharmaceutical oral emulsion. The inventors have unexpectedly found that for the pharmaceutical composition comprising eucalyptol, limonene and alpha-pinene according to the present invention, when the emulsifier and/or co-emulsifier specified in the present invention is used, the resulting oral emulsion has better emulsifying effect, smaller emulsion droplet size, and better centrifugal stability. And other emulsifiers and co-emulsifiers are adopted, so that a good emulsifying effect is difficult to achieve, the particle size of emulsion droplets is large, and more layers are formed after centrifugation. In particular, in a preferred embodiment of the invention, the best effect can be achieved by using a tween 80 and span 80 compound emulsifier as an emulsifier and cooperatively using propylene glycol as a co-emulsifier. The medicinal oral emulsion has good cough relieving, inflammation diminishing and/or phlegm eliminating effects.
The oral emulsion of the medicine has the following characteristics:
1. the medicinal oral emulsion is an oil-in-water emulsion, has small droplet size, is beneficial to accelerating medicament absorption, covering the irritation of volatile oil substances, reducing gastrointestinal adverse reactions and improving the medicament taking compliance of patients;
2. the oral emulsion of the medicine has good centrifugal stability and meets the requirements of pharmacopoeia;
3. the oily medicine is prepared into oral emulsion, which can ensure accurate dosage and is convenient to use;
4. the oral emulsion of the medicine can improve the permeability of the skin and mucous membrane and reduce the irritation.
Detailed Description
The present invention is further illustrated by the following examples, which are illustrative and explanatory only and are not meant to limit the scope of the invention in any way.
The reagents and starting materials used in the following examples are all commercially available.
Example 1
Prescription:
the preparation method comprises the following steps:
(1) mixing soybean oil as oil with eucalyptol, limonene and alpha-pinene to prepare medicated oil;
(2) preparing an emulsifier by adopting Tween 80, span 80 and Tween 20 according to the following weight percentage, wherein:
emulsifier 1 contains span 80 accounting for 18.7 percent and tween 80 accounting for 81.3 percent;
emulsifier 2 contains span 80 of 9.3% and tween 80 of 90.7%;
the emulsifier 3 contains 0.9 percent of span 80 and 99.1 percent of Tween 80;
emulsifier 4 is tween 80;
emulsifier 5 comprises 41.2% of tween 80 and 58.8% of tween 20;
emulsifier 6 is tween 20;
adding the emulsifier and the co-emulsifier 1, 2-propylene glycol into the medicated oil prepared in the step (1) respectively, completely mixing the medicated oil and the emulsifier to form an oil phase, pouring the oil phase into water, uniformly mixing the oil phase and the oil phase without centrifugal operation, and observing the emulsification effect after short-time standing and 24-hour standing, wherein the results are shown in table 1.
TABLE 1 emulsification Effect of different groups of emulsifiers
As can be seen from the results in table 1, tween 80 or tween 20 alone did not give a good emulsifying effect as an emulsifier. The inventor unexpectedly finds that the oral emulsion obtained by using the Tween 80 and span 80 compound emulsifier has the best emulsification effect and has the best stability.
Example 2
Prescription:
the oral medicinal emulsion is prepared from different oils, emulsifiers and auxiliary emulsifiers, and the specific operation process is as follows:
(1) weighing the raw materials, adding eucalyptol, limonene and alpha-pinene into grease, and uniformly mixing to obtain medicated grease;
(2) adding emulsifier and co-emulsifier into the medicated oil, and mixing completely to form oil phase;
(3) pouring the oil phase into purified water, mixing, and making into oral emulsion. Wherein, soybean oil is used as grease, different emulsifiers and coemulsifiers are used for preparing the oral emulsion of the medicine, and the emulsifying effect is observed, and the result is shown in table 2.
TABLE 2 emulsification Effect of pharmaceutical oral emulsions with different emulsifiers, Co-emulsifiers
From the above, the kinds of the emulsifying agent and the co-emulsifying agent have a great influence on the emulsifying effect and the centrifugal stability of the prepared pharmaceutical oral emulsion. The inventor unexpectedly found that when tween 80 and span 80 compound emulsifier is used and 1, 2-propylene glycol is used as co-emulsifier, the obtained oral emulsion has the best emulsification effect and the best centrifugal stability.
According to the formula, the emulsifying effect of the oral pharmaceutical emulsion prepared from different types of oil is as follows, wherein the compound emulsifier of Tween 80 and span 80 (weight ratio is 1: 0.1) is used as an emulsifier, the 12-propylene glycol is used as a co-emulsifier:
table 3: emulsifying effect of oral medicinal emulsion prepared from different oils
Therefore, when the tween 80 and span 80 compound emulsifier is used as the emulsifier and the 1, 2-propylene glycol is used as the co-emulsifier, different oils are used, and better emulsification effect and centrifugal stability can be realized.
Example 3
Prescription:
the preparation process comprises the following steps:
(1) weighing the raw materials according to the proportion of the prescription, adding eucalyptol, limonene and alpha-pinene into soybean oil, uniformly mixing, and stirring for 1 hour at the rotating speed of 50rpm in a constant-temperature water bath at the temperature of 30 ℃ to obtain medicine-containing oil;
(2) adding tween 80 and span 80 (weight ratio 1: 0.07) composite emulsifier and 1, 2-propylene glycol into the medicated oil, stirring in 30 deg.C constant temperature water bath at 50rpm for 2 hr to completely mix to form oil phase;
(3) and dripping the mixed oil phase into purified water under stirring, shearing for 10 minutes at a high-speed shearing machine at the rotating speed of 10000r/min, homogenizing under the pressure of 20bar for 3 minutes after shearing is finished, and thus obtaining the oral emulsion.
The oral emulsion has good emulsifying effect, good centrifugal stability and no layering after centrifugation. The oral emulsion has good antitussive, anti-inflammatory and/or expectorant effects.
Example 4
Prescription:
the preparation process comprises the following steps:
(1) weighing the raw materials according to the proportion, adding eucalyptol, limonene and alpha-pinene into ethyl oleate, uniformly mixing, and stirring for 2 hours in a constant-temperature water bath at 25 ℃ at a rotating speed of 40rpm to obtain medicine-containing oil;
(2) adding tween 80 and span 80 (weight ratio 1: 0.05) composite emulsifier and 1, 2-propylene glycol into the medicated oil, stirring in 25 deg.C constant temperature water bath at 40rpm for 1 hr to completely mix to form oil phase;
(3) adding sucrose and sodium benzoate into purified water, stirring in 25 deg.C constant temperature water bath at 40rpm for 0.5 hr to completely mix to form water phase;
(4) dripping the oil phase into the water phase under stirring, shearing at 10000r/min for 10 min, homogenizing under 20bar for 3 min to obtain oral emulsion.
The oral emulsion has good emulsifying effect, good centrifugal stability and no layering after centrifugation. The oral emulsion has good antitussive, anti-inflammatory and/or expectorant effects.
Example 5
Prescription:
the preparation process comprises the following steps:
(1) weighing the raw materials according to the proportion, adding eucalyptol, limonene and alpha-pinene into soybean oil, uniformly mixing, and stirring for 2 hours in a constant-temperature water bath at 15 ℃ at a rotating speed of 50rpm to obtain medicine-containing oil;
(2) adding tween 80 and span 80 (weight ratio 1: 0.02) composite emulsifier and 1, 2-propylene glycol into the medicated oil, stirring in 15 deg.C constant temperature water bath at 50rpm for 1 hr to completely mix to form oil phase;
(3) adding sweet orange essential oil, potassium sorbate and hydroxymethyl cellulose into purified water, and stirring in a constant temperature water bath at 15 deg.C at 50rpm for 0.5 hr to completely mix to form water phase;
(4) dripping the oil phase into the water phase under stirring, shearing at 10000r/min for 10 min, homogenizing under 20bar for 3 min to obtain oral emulsion.
The oral emulsion has good emulsifying effect, good centrifugal stability and no layering after centrifugation. The oral emulsion has good antitussive, anti-inflammatory and/or expectorant effects.
Example 6
Prescription:
the preparation process comprises the following steps:
(1) weighing the raw materials according to the proportion, adding eucalyptol, limonene and alpha-pinene into medium chain triglyceride, uniformly mixing, and stirring for 2 hours in a constant-temperature water bath at 15 ℃ at a rotating speed of 50rpm to obtain medicine-containing oil;
(2) adding tween 80 and span 80 (weight ratio 1: 0.05) composite emulsifier and 1, 3-propylene glycol into the medicated oil, stirring in 15 deg.C constant temperature water bath at 50rpm for 1 hr to completely mix to form oil phase;
(3) adding stevioside into purified water, and stirring in a constant-temperature water bath at 15 ℃ at a rotating speed of 50rpm for 0.5 hour to completely mix the stevioside and the purified water to form a water phase;
(4) dripping the oil phase into the water phase under stirring, shearing at 10000r/min for 10 min, homogenizing under 20bar for 3 min to obtain oral emulsion.
The oral emulsion has good emulsifying effect, good centrifugal stability and no layering after centrifugation. The oral emulsion has good antitussive, anti-inflammatory and/or expectorant effects.
Example 7
Prescription:
the preparation process comprises the following steps:
(1) weighing the raw materials according to the proportion, adding eucalyptol, limonene and alpha-pinene into soybean oil, uniformly mixing, and stirring for 2 hours in a constant-temperature water bath at 15 ℃ at a rotating speed of 50rpm to obtain medicine-containing oil;
(2) adding tween 80 and span 80 compound emulsifier (weight ratio is 1:0.03) and 1, 2-propylene glycol into the medicated oil, stirring in 15 deg.C constant temperature water bath at 50rpm for 1 hr to completely mix to form oil phase;
(3) dripping the oil phase into the water phase under stirring, shearing at 10000r/min for 10 min, homogenizing under 20bar for 3 min to obtain oral emulsion.
The oral emulsion has good emulsifying effect, good centrifugal stability and no layering after centrifugation. The oral emulsion has good antitussive, anti-inflammatory and/or expectorant effects.
Example 8
Prescription:
the preparation process comprises the following steps:
(1) weighing the raw materials according to the proportion, adding eucalyptol, limonene and alpha-pinene into soybean oil, uniformly mixing, and stirring for 1 hour at the rotating speed of 50rpm in a constant-temperature water bath at the temperature of 30 ℃ to obtain medicine-containing oil;
(2) adding tween 80 and span 80 (weight ratio 1: 0.01) composite emulsifier and 1, 2-propylene glycol into the medicated oil, stirring in 30 deg.C constant temperature water bath at 50rpm for 2 hr to completely mix to form oil phase;
(3) dripping the oil phase into purified water under stirring, performing ultrasonic treatment in an ultrasonic instrument with frequency of 50Hz for 1 hr to obtain primary emulsion, and circulating in a homogenizer at pressure of 50bar for 5 min to obtain oral emulsion.
The oral emulsion has good emulsifying effect, good centrifugal stability and no layering after centrifugation. The oral emulsion has good antitussive, anti-inflammatory and/or expectorant effects.
Examples9
Prescription:
the preparation process comprises the following steps:
(1) weighing the raw materials according to the proportion, adding eucalyptol, limonene and alpha-pinene into soybean oil, uniformly mixing, and stirring for 1 hour at the rotating speed of 60rpm in a constant-temperature water bath at 40 ℃ to obtain medicine-containing oil;
(2) adding tween 80 and span 80 (weight ratio 1: 0.05) composite emulsifier and 1, 2-propylene glycol into the medicated oil, stirring in 30 deg.C constant temperature water bath at 50rpm for 2 hr to completely mix to form oil phase;
(3) dripping the oil phase into purified water under stirring, performing ultrasonic treatment in an ultrasonic instrument with frequency of 40Hz for 2 hr to obtain primary emulsion, and circulating in a homogenizer at 50bar for 5 min to obtain oral emulsion.
The oral emulsion has good emulsifying effect, good centrifugal stability and no layering after centrifugation. The oral emulsion has good antitussive, anti-inflammatory and/or expectorant effects.
Comparative example 1
Prescription:
the preparation process comprises the following steps:
(1) weighing the raw materials according to the proportion, adding eucalyptol, limonene and alpha-pinene into soybean oil, uniformly mixing, and stirring for 1 hour at the rotating speed of 60rpm in a constant-temperature water bath at 40 ℃ to obtain medicine-containing oil;
(2) adding tween 80 and 1, 2-propylene glycol into the medicated oil, and stirring in 30 deg.C constant temperature water bath at 50rpm for 2 hr to completely mix to form oil phase;
(3) dripping the oil phase into purified water under stirring, performing ultrasonic treatment in an ultrasonic instrument with frequency of 40Hz for 2 hr to obtain primary emulsion, and circulating in a homogenizer at 50bar for 5 min to obtain oral emulsion.
The oral emulsion is separated obviously after centrifugation.
The formulation and process of comparative example 1 and example 9 were the same except that the type of emulsifier used was different. As can be seen from the experimental results, the particle size of the emulsion after emulsification using tween 80, which is a single emulsifier, of comparative example 1 was significantly increased, and the centrifugal stability of the emulsion was poor, compared to example 9. Therefore, the Tween 80 and span 80 compound emulsifier is preferably adopted as the emulsifier, the centrifugal stability of the emulsion is unexpectedly and remarkably improved, and the particle size of emulsion droplets is remarkably reduced.
As can be seen from the above examples, the pharmaceutical oral emulsion of the present invention has the following characteristics:
1. the medicinal oral emulsion is an oil-in-water emulsion, has small droplet size, is beneficial to accelerating medicament absorption, covering the irritation of volatile oil substances, reducing gastrointestinal adverse reactions and improving the medicament taking compliance of patients;
2. the oral emulsion of the medicine has good centrifugal stability and meets the requirements of pharmacopoeia;
3. the oily medicine is prepared into oral emulsion, which can ensure accurate dosage and is convenient to use;
4. the oral emulsion of the medicine can improve the permeability of the skin and mucous membrane and reduce the irritation.
Claims (10)
1. A pharmaceutical oral emulsion, which comprises a pharmaceutical composition consisting of eucalyptol, limonene and alpha-pinene, and an emulsifier, wherein the emulsifier is selected from two or more of tween 80, tween 20, span 80, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil and poloxamer 188.
2. The pharmaceutical oral emulsion of claim 1, wherein the emulsifier is a tween 80 and span 80 complex emulsifier.
3. The pharmaceutical oral emulsion according to claim 1 or 2, wherein the emulsifier is present in an amount of 3.0 to 6.0%, preferably 4.0 to 5.5%, based on the weight of the pharmaceutical oral emulsion.
4. The pharmaceutical oral emulsion of claim 1, further comprising a co-emulsifier selected from one or more of ethanol, propylene glycol, glycerol and polyethylene glycol, preferably one or more of propylene glycol, glycerol and polyethylene glycol 400, more preferably propylene glycol, most preferably 1, 2-propylene glycol.
5. The pharmaceutical oral emulsion of claim 4, wherein the co-emulsifier is present in an amount of 1.0 to 3.0%, preferably 1.2 to 1.8%, based on the weight of the pharmaceutical oral emulsion.
6. The pharmaceutical oral emulsion of claim 1, wherein the pharmaceutical composition further comprises oil and water; preferably, the oil or fat is selected from one or more of soybean oil, medium chain triglycerides and ethyl oleate, most preferably soybean oil.
7. The pharmaceutical oral emulsion of claim 1, wherein the pharmaceutical composition is present in an amount of 5.0 to 20.0%, preferably 5.0 to 13.0%, based on the weight of the pharmaceutical oral emulsion.
8. The pharmaceutical oral emulsion of claim 7, wherein the oil is present in an amount of 1.0 to 8.0% and the water is present in an amount of 72.0 to 85.0% based on the weight of the pharmaceutical oral emulsion; preferably, the content of the grease is 3.0-5.0%, and the content of the water is 75.0-82.0%.
9. The pharmaceutical oral emulsion of claim 1, wherein the pharmaceutical composition consists of, based on the weight of the pharmaceutical composition, 40.0 to 65.0% eucalyptol, 20.0 to 45.0% limonene and 5.0 to 25.0% alpha-pinene.
10. Use of the pharmaceutical oral emulsion of any one of claims 1 to 9 in the manufacture of a medicament for cough suppression, inflammation reduction and/or phlegm elimination.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911022519.9A CN112791120B (en) | 2019-10-25 | 2019-10-25 | A pharmaceutical oral emulsion, and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911022519.9A CN112791120B (en) | 2019-10-25 | 2019-10-25 | A pharmaceutical oral emulsion, and its preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112791120A true CN112791120A (en) | 2021-05-14 |
| CN112791120B CN112791120B (en) | 2023-08-01 |
Family
ID=75802900
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911022519.9A Active CN112791120B (en) | 2019-10-25 | 2019-10-25 | A pharmaceutical oral emulsion, and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112791120B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112704674A (en) * | 2019-10-25 | 2021-04-27 | 北京远大九和药业有限公司 | Oral emulsion and its prepn and use |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101015524A (en) * | 2007-02-15 | 2007-08-15 | 沈阳药科大学 | Coenzyme Q10 oral emulsion and preparing process thereof |
| CN101502488A (en) * | 2009-03-13 | 2009-08-12 | 沈阳药科大学 | Teniposide emulsion and preparation method thereof |
| CN103655710A (en) * | 2012-09-05 | 2014-03-26 | 北京因科瑞斯医药科技有限公司 | Nux vomica total alkali micro-emulsion, preparation thereof and preparation methods of nux vomica total alkali micro-emulsion and preparation |
| CN106389329A (en) * | 2016-12-05 | 2017-02-15 | 黑龙江童医生儿童生物制药有限公司 | Dipyridamole oral emulsion administration system and preparation method thereof |
| CN109528649A (en) * | 2019-01-15 | 2019-03-29 | 北京远大九和药业有限公司 | A kind of terpenes pharmaceutical composition self-emulsifiable oral preparation and preparation method, application |
-
2019
- 2019-10-25 CN CN201911022519.9A patent/CN112791120B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101015524A (en) * | 2007-02-15 | 2007-08-15 | 沈阳药科大学 | Coenzyme Q10 oral emulsion and preparing process thereof |
| CN101502488A (en) * | 2009-03-13 | 2009-08-12 | 沈阳药科大学 | Teniposide emulsion and preparation method thereof |
| CN103655710A (en) * | 2012-09-05 | 2014-03-26 | 北京因科瑞斯医药科技有限公司 | Nux vomica total alkali micro-emulsion, preparation thereof and preparation methods of nux vomica total alkali micro-emulsion and preparation |
| CN106389329A (en) * | 2016-12-05 | 2017-02-15 | 黑龙江童医生儿童生物制药有限公司 | Dipyridamole oral emulsion administration system and preparation method thereof |
| CN109528649A (en) * | 2019-01-15 | 2019-03-29 | 北京远大九和药业有限公司 | A kind of terpenes pharmaceutical composition self-emulsifiable oral preparation and preparation method, application |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112704674A (en) * | 2019-10-25 | 2021-04-27 | 北京远大九和药业有限公司 | Oral emulsion and its prepn and use |
| CN112704674B (en) * | 2019-10-25 | 2024-03-12 | 北京远大九和药业有限公司 | A pharmaceutical oral emulsion, and its preparation method and application |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112791120B (en) | 2023-08-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI325325B (en) | Nanoliposome using esterified lecithin and method for preparing the same, and composition for preventing or treating skin diseases comprising the same | |
| US20190282513A1 (en) | Compound for use in relief of pain and method to produce thereof | |
| JPH1036276A (en) | Antiallergic agent and antiallergic cosmetic material and food containing the same | |
| EP2273987A2 (en) | Film-shaped preparation comprising oily substances for oral administration | |
| EP3689328A1 (en) | Compositions for relieving pain comprising malkangni oil and cypriol oil as active ingredients | |
| CN113056257A (en) | Semisolid oil-based pharmaceutical composition containing pirfenidone for tissue repair | |
| CN112791120B (en) | A pharmaceutical oral emulsion, and its preparation method and application | |
| KR100722677B1 (en) | Cosmetic composition for high internal phase water-in-oil type emulsion | |
| JP2002326920A (en) | Emulsion composition | |
| US20130039978A1 (en) | Medicinal compositions and method for treatment of urinary tract infections | |
| JPS597106A (en) | Emulsifiable composition | |
| CN114642635B (en) | Oral emulsion of terpene medicine composition and preparation method and application thereof | |
| CN112704674B (en) | A pharmaceutical oral emulsion, and its preparation method and application | |
| US11478446B2 (en) | Pain relieving formulations containing cannabis and methods of making same | |
| WO2023278708A1 (en) | Methods for treatment of pain with cannabinoids | |
| CN115518030A (en) | Preparation method of dimethicone cream | |
| CN109758542B (en) | Compound costus root oil fat emulsion preparation with stomach invigorating effect, and preparation method and application thereof | |
| CN102949415B (en) | Propolis fat emulsion preparation and preparation method thereof | |
| JPS59141510A (en) | Emulsified composition | |
| JP2020011993A (en) | Skin external application agent | |
| EP2994166B1 (en) | Aqueous gels with diethylether | |
| WO2019086195A1 (en) | Process for preparing topical formulations by means of ultrasound and formulations so obtained | |
| US20230255900A1 (en) | Compositions for topical treatment of radiation dermatitis | |
| JP4615814B2 (en) | Liquid external preparation for cold medicine and method for producing the same | |
| JP7398589B1 (en) | External pain relief preparation containing ginger ingredients |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |