CN1180767C - Soluble liquide preparation of liposoluble matter - Google Patents
Soluble liquide preparation of liposoluble matter Download PDFInfo
- Publication number
- CN1180767C CN1180767C CNB011259159A CN01125915A CN1180767C CN 1180767 C CN1180767 C CN 1180767C CN B011259159 A CNB011259159 A CN B011259159A CN 01125915 A CN01125915 A CN 01125915A CN 1180767 C CN1180767 C CN 1180767C
- Authority
- CN
- China
- Prior art keywords
- tocopherol
- soluble
- liquide
- polyoxyethylene
- preparation
- 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.)
- Expired - Fee Related
Links
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- -1 polyoxyethylene Polymers 0.000 claims abstract description 89
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 239000008213 purified water Substances 0.000 claims abstract description 24
- 238000004519 manufacturing process Methods 0.000 claims abstract description 10
- 229920001214 Polysorbate 60 Polymers 0.000 claims abstract description 8
- 150000005215 alkyl ethers Chemical class 0.000 claims abstract description 8
- 229930006000 Sucrose Natural products 0.000 claims abstract description 6
- 238000010790 dilution Methods 0.000 claims abstract description 6
- 239000012895 dilution Substances 0.000 claims abstract description 6
- 239000005720 sucrose Substances 0.000 claims abstract description 6
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- PFRQBZFETXBLTP-RCIYGOBDSA-N 2-[(2e,6e,10e,14e,18e)-3,7,11,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaen-1-yl]-3-methyl-1,4-dihydronaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)=C(C)C(=O)C2=C1 PFRQBZFETXBLTP-RCIYGOBDSA-N 0.000 description 1
- 241001071795 Gentiana Species 0.000 description 1
- MJVAVZPDRWSRRC-UHFFFAOYSA-N Menadione Chemical compound C1=CC=C2C(=O)C(C)=CC(=O)C2=C1 MJVAVZPDRWSRRC-UHFFFAOYSA-N 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003221 ear drop Substances 0.000 description 1
- 229940047652 ear drops Drugs 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- MBWXNTAXLNYFJB-LKUDQCMESA-N phylloquinone Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CCCC(C)CCCC(C)CCCC(C)C)=C(C)C(=O)C2=C1 MBWXNTAXLNYFJB-LKUDQCMESA-N 0.000 description 1
- 239000011772 phylloquinone Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 230000035943 smell Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940045613 taurine 1000 mg Drugs 0.000 description 1
- 229930003802 tocotrienol Natural products 0.000 description 1
- 239000011731 tocotrienol Substances 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Classifications
-
- 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
- A61K9/08—Solutions
-
- 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
- A61K31/352—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 condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A solubilizing liquid agent having a good stability, high transparency, and containing a good taste and flavor fat-soluble matter, more particularly, an internal use soluble liquid agent of a tonic and so on is provided. The solubilizing liquid agent comprises: a fat-soluble matter; (1) greater than 50 wt% and less than 100 wt% of one or two more of polyoxyethylene curing castor oil and polyoxyethylene castor oil based on the fat-soluble matter, (2) 5 to 100 wt% of one or two more of polyglycerol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester, sucrose fatty acid ester and polyoxyethylene alkyl ether based on the fat-soluble matter, and (3) 10 to 80 wt% of polyatomic alcohol based on the total amount of the solubilizing liquid agent. In addition, a manufacturing method of the solubilizing liquid agent and a solubilizing liquid agent dilution formed by diluting the solubilizing liquid agent with purified water, buffer solution or aqueous liquid agent.
Description
Technical field
The present invention relates to contain liposoluble substance, taste and take excellent and high soluble liquide preparation and the manufacture method thereof of the stable outstanding transparency of sensation.
Background technology
General liposoluble substance is an indissoluble for water, and for liposoluble substance being made the soluble liquide preparation of mixture for internal use or aqueous injection etc., people have carried out various trials.
For example, the vitamin E that uses liposoluble substance is disclosed in special fair 4-7722 number, contain (A) vitamin E, (B) but be the hardened castor oil polyoxyethylene deriv of 100-500 weight % and (C) be that one or more of 10-50 weight % are selected from the stable vitamin E dissolving liquid of the stabilizing agent of sorbitan fatty acid ester, polyoxyethylene sorbitol fatty acid ester, polyglyceryl fatty acid ester and polyoxyethylene fatty acid glyceride with respect to vitamin E with respect to vitamin E.
But, but this vitamin E dissolving liquid, owing to particularly must add with respect to vitamin E is the so very a large amount of surfactant (hardened castor oil polyoxyethylene deriv) of hardened castor oil polyoxyethylene deriv of 100-500 weight %, so wish to reduce aspects such as additive intake, be desired hardly from manufacturing cost or consumer.In addition, but should dissolving liquid can feel strongly that by the material that can optimize the transparency be the bad taste of hardened castor oil polyoxyethylene deriv origin, therefore as mixture for internal use, its taste and to take sense all bad.
In containing the soluble liquide preparation of liposoluble substance, people expect to develop outstanding, the transparent height of stability and taste and take the outstanding soluble liquide preparation of sense.Water solublity liquor for oral administration such as oral liquid particularly.In addition, oral liquid is many to be taken as tonic invigorator, therefore as liposoluble substance, contains fatsoluble vitamin, particularly vitamin E class, retinoid, vitamin D class and/or vitamin K class, bad taste is arranged, people expectation does not have the soluble liquide preparation of this not well tasting.
Summary of the invention
The present invention relates to contain liposoluble substance and (1) with respect to more than the liposoluble substance 50 weight %, be less than a kind of of 100 weight % or be selected from polyoxyethylene hardened castor oil and polyoxyethylene castor oil more than 2 kinds, (2) with respect to a kind of of liposoluble substance 5-100 weight % or be selected from polyglyceryl fatty acid ester more than 2 kinds, polyoxyethylene sorbitan fatty acid ester, the polyoxyethylene fatty acid glyceride, sucrose fatty acid ester and polyoxyethylene alkyl ether, (3) soluble liquide preparation and the manufacture method thereof of the liposoluble substance that forms with respect to the polyhydric alcohol of soluble liquide preparation total amount 10-80 weight %, and with this soluble liquide preparation purified water, the soluble liquide preparation diluent of the liposoluble substance that contains 0.01-0.3 weight % that buffer or the dilution of aqueous liquor form.
The specific embodiment
In soluble liquide preparation of the present invention, as the polyoxyethylene hardened castor oil and/or the polyoxyethylene castor oil of (1), the material that the average addition molal quantity of optimization ethylene oxide is 40-60.The combined amount of this polyoxyethylene hardened castor oil and/or polyoxyethylene castor oil, in order to obtain enough transparencys and good taste and to take sense, should be to be, to be less than 100 weight % more than the 50 weight % with respect to liposoluble substance, preferred 70 weight % are above, be less than 100 weight %, and more preferably 80 weight % are to 100 weight %.
In addition, in soluble liquide preparation of the present invention, as the fatty acid ester of (2), the ester of the saturated or unsaturated fatty acid of preferred carbon number 14-22 can be the ester of partial esterification or complete esterification.In addition, the glycerol polymerization degree of polyglyceryl fatty acid ester is preferably 2-10, and the average addition molal quantity of the oxirane of polyoxyethylene sorbitan fatty acid ester and polyoxyethylene fatty acid glyceride is preferably 6-40.In addition, the carbon number of the alkyl of polyoxyethylene alkyl ether is preferably 12-22, and the average addition molal quantity of oxirane is preferably 6-40.
Combined amount that should (2) composition in order to obtain enough transparencys and good taste and to take sense, should be to be 5-100 weight % with respect to liposoluble substance, preferred 10-50 weight %.
The liposoluble substance that the present invention relates to, have no particular limits, for example, specifiable have, fatsoluble vitamiies such as vitamin E class, retinoid, beta-carotene, vitamin D class and/or vitamin K class, crotamiton, teprenone, indometacin, prednisolone, tannic acid etc., preferred vitamin E class, retinoid, vitamin D class and/or vitamin K class, more preferably vitamin E class.
As the vitamin E class, for example, specifiable have, the dl-alpha-tocopherol, the d-alpha-tocopherol, acetic acid dl-alpha-tocopherol, acetic acid d-alpha-tocopherol, succinic acid dl-alpha-tocopherol, succinic acid d-alpha-tocopherol, nicotinic acid dl-alpha-tocopherol, nicotinic acid d-alpha-tocopherol, the dl-betatocopherol, the d-betatocopherol, acetic acid dl-betatocopherol, acetic acid d-betatocopherol, succinic acid dl-betatocopherol, succinic acid d-betatocopherol, nicotinic acid dl-betatocopherol, nicotinic acid d-betatocopherol, the dl-Gamma-Tocopherol, the d-Gamma-Tocopherol, acetic acid dl-Gamma-Tocopherol, acetic acid d-Gamma-Tocopherol, succinic acid dl-Gamma-Tocopherol, succinic acid d-Gamma-Tocopherol, nicotinic acid dl-Gamma-Tocopherol, nicotinic acid d-Gamma-Tocopherol, the dl-Delta-Tocopherol, the d-Delta-Tocopherol, acetic acid dl-Delta-Tocopherol, acetic acid d-Delta-Tocopherol, succinic acid dl-Delta-Tocopherol, succinic acid d-Delta-Tocopherol, nicotinic acid dl-Delta-Tocopherol, nicotinic acid d-Delta-Tocopherol, tocotrienol etc.Preferred acetic acid d-alpha-tocopherol.As the vitamin D class, for example, vitamin D
1, vitamin D
2, vitamin D
3, as the vitamin K class, specifiable have, vitamin K
1, vitamin K
2, vitamin K
3, vitamin K
4Deng.
Among the present invention in the soluble liquide preparation content of liposoluble substance have no particular limits, be 3-15 weight % preferably with respect to the soluble liquide preparation total amount.
As the polyhydric alcohol among the present invention, for example, specifiable have, glycerol, diglycerol, two triglycerols, polyglycereol, propylene glycol, dipropylene glycol, 1,3 butylene glycol, ethylene glycol, Polyethylene Glycol, Sorbitol, mannitol, xylitol etc.The combined amount of polyhydric alcohol from guaranteeing enough transparencys and guarantee the viewpoint of the suitable combined amount of liposoluble substance (1) and (2) composition, should be to be 10-80 weight % with respect to the soluble liquide preparation total amount, preferably 30-80 weight %.
Soluble liquide preparation of the present invention has or not the mixing of purified water to make.Since can make the viscosity of soluble liquide preparation reduce by mixing purified water, therefore can be by adding purified water, and operability is good during fabrication to make soluble liquide preparation.
The soluble liquide preparation of liposoluble substance of the present invention can be used as 1) oral liquid, liquor, syrup, gargarism, oral medicine such as mouthwash, health product, 2) elixir, lotion, drop, nasal drop, eardrops, transvaginal is given medicament, through medicine for external use, health product such as enteral administration agent, the cosmetics compounding ingredient, or 3) adding conventional excipients formation tablet, masticatory, granule, solid preparations such as capsule use.
The soluble liquide preparation of liposoluble substance of the present invention, but former state is taken, and particularly when using as mixture for internal use such as oral liquids, can further add purified water, aqueous such as buffer or oral liquid liquor is diluted to any concentration, as the diluent use of soluble liquide preparation.Concentration for liposoluble substance in the soluble liquide preparation diluent has no particular limits, preferred 0.01-0.3 weight %.
Make soluble liquide preparation of the present invention, above-mentioned each composition can be mixed, modulation contains each mixture of ingredients, also can further carry out HIGH PRESSURE TREATMENT with containing each mixture of ingredients.
Therefore, the invention provides the manufacture method of the soluble liquide preparation of liposoluble substance, it is characterized in that, in liposoluble substance, mix (1) with respect to more than the liposoluble substance 50 weight %, be less than a kind of of 100 weight % or be selected from polyoxyethylene hardened castor oil and polyoxyethylene castor oil more than 2 kinds, (2) with respect to a kind of of liposoluble substance 5-100 weight % or be selected from polyglyceryl fatty acid ester more than 2 kinds, polyoxyethylene sorbitan fatty acid ester, the polyoxyethylene fatty acid glyceride, the material of sucrose fatty acid ester and polyoxyethylene alkyl ether, then, mix (3) polyhydric alcohol, or mixed mixture is carried out HIGH PRESSURE TREATMENT with respect to soluble liquide preparation total amount 10-80 weight %.
Temperature when above-mentioned each composition mixes is preferably 60-90 ℃, more preferably 70-85 ℃.In addition, when each composition mixes, can use simple blender such as propeller type, anchor formula, and/or high-shear emulsifying machines such as homogenizer, homogenizer etc.
HIGH PRESSURE TREATMENT is used high pressure homogenizer, the mulser etc. that pressurizes at a high speed usually.The temperature of liquor is generally from extremely about 90 ℃ of room temperature, preferred 60-80 ℃ during HIGH PRESSURE TREATMENT.In addition, the pressure during for HIGH PRESSURE TREATMENT has no particular limits, and is generally 100-5000kg/cm
2(9807-490350kPa), preferred 150-2000kg/cm
2(19614-196140kPa), more preferably 200-1800kg/cm
2(29421-17656kPa).
The soluble liquide preparation of liposoluble substance of the present invention is the outstanding and transparent high liquor of stability.Particularly the addition of surfactant polyoxyethylene hardened castor oil and/or polyoxyethylene castor oil is to be more than the 50 weight %, to be less than the considerably less like this amount of 100 weight % with respect to liposoluble substance, the present invention is had can obtain the high such marked feature of liquor of the transparency.In addition, the soluble liquide preparation of liposoluble substance of the present invention, almost imperceptible bad taste when taking has at taste and takes very outstanding this marked feature aspect the sense.
In the prior art that the soluble liquide preparation of liposoluble substance relates to, in order to obtain having the high liquor of transmitance of enough transparencys, the surfactants such as macro-mixing polyoxyethylene hardened castor oil of having to, in addition, because its combined amount is many, existence can be felt strongly by this surfactant bad taste that brings and the problem of taking sense.The soluble liquide preparation of liposoluble substance of the present invention, be reduced to specific scope by combined amount with surfactants such as polyoxyethylene hardened castor oils, solve the problems referred to above, thereby reached the enough solution transparency and the good taste of transmitance more than 90%, take and feel the remarkable result that two aspects have both.
Therefore, the soluble liquide preparation of the liposoluble substance that the present invention relates to, and the soluble liquide preparation diluent that soluble liquide preparation is obtained with purified water, buffer or the dilution of aqueous liquor, particularly useful in use occasions such as medicines such as oral liquid, liquor, syrup, gargarism, mouthwash, health product.
The soluble liquide preparation of liposoluble substance of the present invention and soluble liquide preparation diluent for example can be made as follows.
For example, add acetic acid d-alpha-tocopherol 100g, polyoxyethylene hardened castor oil 85g, polyglyceryl fatty acid ester 30g, glycerol 635g and purified water 150g mix, and when heating to about 70 ℃, minute mix in homogenizer 10000rpm * 5, be modulated into the aqueous liquor of homogeneous, can make the soluble liquide preparation of acetic acid d-alpha-tocopherol.In addition, further this aqueous liquor is used the high pressure homogenizer, at 1000kg/cm
2(98070kPa) carry out HIGH PRESSURE TREATMENT, also can make the soluble liquide preparation of acetic acid d-alpha-tocopherol.In addition, in this soluble liquide preparation 1g, add the buffer that transfers to pH3 and dilute, can make the soluble liquide preparation diluent that contains 0.1 weight % acetic acid d-alpha-tocopherol.
According to the present invention, can provide and contain liposoluble substance, taste feels outstanding with taking, and stability is outstanding, the soluble liquide preparation that the transparency is high.
Embodiment
The present invention will be described in more detail to enumerate embodiment below, but the present invention is not limited to these embodiment.
Embodiment 1-embodiment 8
Use acetic acid d-alpha-tocopherol as liposoluble substance, mix each component, when heating, minute mix, be modulated into the soluble liquide preparation of homogeneous in homogenizer 10000rpm * 5 to about 70 ℃ according to prescription shown in the table 1.This aqueous liquor is used the high pressure homogenizer, at 1000kg/cm
2(98070kPa) carry out HIGH PRESSURE TREATMENT, obtain the soluble liquide preparation of acetic acid d-alpha-tocopherol.
In the gained soluble liquide preparation, add entry, dilute, put into specific container, measure averaged particles footpath (nm) with submicron particle assay device (Coulter company makes, MODEL N4 SD) for population 100000-1000000/ml.
In addition, in the soluble liquide preparation 1g that above-mentioned HIGH PRESSURE TREATMENT is crossed, add commercially available oral liquid (A) 100mL and (contain nicotiamide 20mg among 1 bottle of 100mL, taurine 1g, thiamine nitrate 5mg, Riboflavin Sodium Phosphate 5mg, benadon 5mg, hydrochloric acid carnitine 100mg, inositol 50mg, Caffeine Anhydrous 50mg) dilute, can obtain acetic acid d-alpha-tocopherol content is the soluble liquide preparation diluent of 100mg.
Comparative example 1
Use acetic acid d-alpha-tocopherol as liposoluble substance, except according to prescription (add with respect to liposoluble substance 200 weight % polyoxyethylene hardened castor oil) shown in the table 1, mix each component, all the other and embodiment 1-8 operate equally, the soluble liquide preparation and the acetic acid d-alpha-tocopherol content that obtain acetic acid d-alpha-tocopherol are the soluble liquide preparation diluent of 100mg, measure mean diameter equally.
The soluble liquide preparation diluent that soluble liquide preparation diluent that embodiment 1-8 is obtained and comparative example obtain is made comparisons, and carries out evaluation of physical property.Evaluation is after manufacturing just, after 1 day and 7 days, measures transmitance (%) at 640nm 70 ℃ of preservations, respectively the soluble liquide preparation diluent is included for 5 seconds in the oral cavity after just having made, and carries out taste and the functional check of taking sense, estimates according to following benchmark.Prescription and each result of the test are as shown in table 1.
＜taste and take the metewand of sense
Zero: taste feels good with taking.
△: can feel taste and to take sense poor slightly.
*: can feel taste and take the sense bad.
Table 1
| Embodiment | Comparative example | |||||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 1 | ||
| Prescription (%) | Acetic acid D-alpha-tocopherol | 10.0 | 10.0 | 10.0 | 10.0 | 10.0 | 10.0 | 10.0 | 10.0 | 10.0 |
| SY-Glyster MSW 750 | 5.0 | 4.0 | 3.0 | 2.0 | 1.0 | 5.7 | 5.0 | 5.0 | 5.7 | |
| Polyoxyethylene hardened castor oil 60 | 8.5 | 8.5 | 8.5 | 8.5 | 8.5 | 10.0 | 7.0 | 6.0 | 20.0 | |
| Glycerol | 61.5 | 62.5 | 63.5 | 64.5 | 65.5 | 59.3 | 63.0 | 64.0 | 49.3 | |
| Purified water | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | |
| Add up to | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | |
| Averaged particles footpath (nm) | 48.5 | 50.7 | 51.7 | 54.2 | 58.1 | 45.4 | 52.1 | 65.6 | 45.4 | |
| Transmitance (%) | After just having made | 97.6 | 96.2 | 95.3 | 95.9 | 92.3 | 97.8 | 96.2 | 93.4 | 98.8 |
| Preserved 1 day for 70 ℃ | 97.4 | 96.2 | 95.9 | 96.4 | 94.1 | 94.1 | 96.2 | 93.8 | 98.6 | |
| Preserved 7 days for 70 ℃ | 94.5 | 93.7 | 936.6 | 93.7 | 91.9 | 94.1 | 94.0 | 91.4 | 96.7 | |
| Organoleptic test's (taste and take sense) | ○ | ○ | ○ | ○ | ○ | ○ | ○ | ○ | × | |
As known from Table 1, arbitrary product of embodiment 1-8 all is " taste of liquor and take sense good ".On the other hand, the mixed proportion of polyoxyethylene hardened castor oil is with respect to the comparative example 1 of liposoluble substance 200 weight %, can feel " taste and take sense bad ".
In addition, the soluble liquide preparation diluent is in the transmitance (%) of 640nm, and is as shown in table 1, and after making, each embodiment has the good transparency more than 90%, in addition, even preserved 1 day and 7 days at 70 ℃, also do not observe transmitance and significantly reduces.And, because the difference that the mixed proportion of polyoxyethylene hardened castor oil or polyglyceryl fatty acid ester (SY-Glyster MSW 750) causes does not almost have, though can confirm to have how many tendencies that can uprise of the big more transmitance of cooperation ratio, can not think to have very big difference.In addition, usually, if the transmitance of liquor is more than 90%, can judge to have enough transparencys in appearance, even the embodiment 5 of the mixed proportion minimum of polyglyceryl fatty acid ester (is 10 weight % with respect to liposoluble substance), the transmitance after just making is 92.3%, be respectively 94.1% in the transmitance of 70 ℃ of preservations after 1 day and 7 days, 91.9%, from having the transparency with comparative example 1 same degree in appearance, also we can say to have the good transparency.
From the front as can be known,, can obtain containing liposoluble substance according to the present invention, taste and to take sense outstanding, and stability is outstanding, the soluble liquide preparation that the transparency is high.
Embodiment 9-embodiment 13
Use acetic acid d-alpha-tocopherol as liposoluble substance, mix each component, when heating, minute mix, be modulated into the soluble liquide preparation of homogeneous in homogenizer 10000rpm * 5 to about 70 ℃ according to prescription shown in the table 2.This aqueous liquor is used the high pressure homogenizer, at 300kg/cm
2(29421kPa) carry out HIGH PRESSURE TREATMENT, obtain the soluble liquide preparation of acetic acid d-alpha-tocopherol.The averaged particles footpath of gained soluble liquide preparation is measured according to the same quadrat method of embodiment 1-8.
In addition, in the soluble liquide preparation 1g that above-mentioned HIGH PRESSURE TREATMENT is crossed, add commercially available oral liquid (A) 100mL and (contain nicotiamide 20mg among 1 bottle of 100mL, taurine 1g, thiamine nitrate 5mg, Riboflavin Sodium Phosphate 5mg, benadon 5mg, hydrochloric acid carnitine 100mg, inositol 50mg, Caffeine Anhydrous 50mg) dilute, can obtain acetic acid d-alpha-tocopherol content is the soluble liquide preparation diluent of 100mg.Gained soluble liquide preparation diluent is measured transmitance according to the same quadrat method of embodiment 1-8, check taste and take sense.Prescription and result of the test are as shown in table 2.
Table 2
| Embodiment | ||||||
| 9 | 10 | 11 | 12 | 13 | ||
| Prescription (%) | Acetic acid d-alpha-tocopherol | 10.0 | 10.0 | 10.0 | 10.0 | 10.0 |
| Polyoxyethylene (20) sorbitan monostearate | 5.0 | - | 3.0 | - | - | |
| Polyoxyethylene (25) lauryl ether | - | 5.0 | - | 3.0 | - | |
| SY-Glyster MSW 750 | - | - | - | - | 5.0 | |
| Polyoxyethylene hardened castor oil 60 | 8.5 | 8.5 | 8.5 | 8.5 | - | |
| Polyoxyethylene hardened castor oil 40 | - | - | - | - | 10.0 | |
| Glycerol | 61.5 | 61.5 | 63.5 | 63.5 | 50.0 | |
| Purified water | 15.0 | 15.0 | 15.0 | 15.0 | 25.0 | |
| Add up to | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | |
| Averaged particles footpath (nm) | 44.7 | 47.8 | 44.4 | 42.1 | - | |
| Transmitance (%) | After just having made | 96.0 | 97.9 | 98.0 | 98.2 | 94.3 |
| Preserved 1 day for 70 ℃ | 97.9 | 97.8 | 98.0 | 98.0 | - | |
| Preserved 7 days for 70 ℃ | 94.4 | 95.2 | 95.6 | 94.9 | 95.3 | |
| Organoleptic test's (taste and take sense) | ○ | ○ | ○ | ○ | ○ | |
As known from Table 2, the transmitance of arbitrary embodiment after just making all is more than 90%, has the good transparency, and even 70 ℃ of preservations, transmitance does not significantly reduce yet.And taste feels good with taking.
Embodiment 14-embodiment 16
Use acetic acid d-alpha-tocopherol as liposoluble substance, mix each component, when heating, minute mix, be modulated into the soluble liquide preparation of homogeneous in homogenizer 10000rpm * 5 to about 70 ℃ according to prescription shown in the table 3.This aqueous liquor is used the high pressure homogenizer, at 200kg/cm
2(19614kPa) carry out HIGH PRESSURE TREATMENT, obtain the soluble liquide preparation of acetic acid d-alpha-tocopherol.The averaged particles footpath of gained soluble liquide preparation is measured according to the same quadrat method of embodiment 1-8.
In addition, in the soluble liquide preparation 1g that above-mentioned HIGH PRESSURE TREATMENT is crossed, add commercially available oral liquid (A) 100mL and (contain nicotiamide 20mg among 1 bottle of 100mL, taurine 1g, thiamine nitrate 5mg, Riboflavin Sodium Phosphate 5mg, benadon 5mg, hydrochloric acid carnitine 100mg, inositol 50mg, Caffeine Anhydrous 50mg) dilute, can obtain acetic acid d-alpha-tocopherol content is 120mg (embodiment 14), the soluble liquide preparation diluent of 150mg (embodiment 15-embodiment 16).Gained soluble liquide preparation diluent is measured transmitance according to the same quadrat method of embodiment 1-8, check taste and take sense.Prescription and result of the test are as shown in table 3.
Table 3
| Embodiment | ||||
| 14 | 15 | 16 | ||
| Prescription (%) | Acetic acid d-alpha-tocopherol | 12.0 | 15.0 | 15.0 |
| SY-Glyster MSW 750 | 5.0 | 5.0 | 5.0 | |
| Polyoxyethylene hardened castor oil 60 | 10.0 | 10.0 | 12.0 | |
| Glycerol | 58.0 | 55.0 | 53.0 | |
| Purified water | 15.0 | 15.0 | 15.0 | |
| Add up to | 100.0 | 100.0 | 100.0 | |
| Averaged particles footpath (nm) | 50.0 | 64.7 | 52.1 | |
| Transmitance (%) | After just having made | 97.1 | 92.7 | 93.8 |
| Preserved 1 day for 70 ℃ | 94.6 | 93.2 | 93.3 | |
| Preserved 7 days for 70 ℃ | 93.9 | 91.0 | 92.2 | |
| Organoleptic test's (taste and take sense) | ○ | ○ | ○ | |
As known from Table 3, irrelevant with the concentration of vitamin E, the transmitance of embodiment 14,15 and 16 soluble liquide preparation diluent all is more than 90% after just making, and has the good transparency.In addition, even 70 ℃ of preservations, transmitance does not significantly reduce yet.And taste feels good with taking.
Embodiment 17-19
Use acetic acid d-alpha-tocopherol as liposoluble substance, mix each component, when heating, minute mix, be modulated into the soluble liquide preparation of homogeneous in homogenizer 10000rpm * 10 to about 80 ℃ according to prescription shown in the table 4.This aqueous liquor is used the high-pressure emulsification machine, carry out HIGH PRESSURE TREATMENT, be cooled to room temperature, obtain the soluble liquide preparation of acetic acid d-alpha-tocopherol at 9000psi.Further add commercially available oral liquid (A) according to the same quadrat method of embodiment 1-8 and dilute, obtaining acetic acid d-alpha-tocopherol content is the soluble liquide preparation diluent of 100mg.
Gained soluble liquide preparation diluent is measured transmitance, averaged particles footpath according to the same quadrat method of embodiment 1-8, check taste and take sense.Prescription and result of the test are as shown in table 4.
Table 4
| Embodiment | ||||
| 17 | 18 | 19 | ||
| Prescription (%) | Acetic acid-d-alpha-tocopherol | 10 | 10 | 10 |
| SY-Glyster MSW 750 | 5 | 5 | 5 | |
| Polyoxyethylene hardened castor oil 60 | 8.5 | 8.5 | 8.5 | |
| Glycerol | 60 | 55 | 50 | |
| Purified water | 16.5 | 21.5 | 26.5 | |
| Add up to | 100 | 100 | 100 | |
| Transmitance (%) | After just having made | 95.9 | 95.7 | 94.9 |
| Preserved 7 days for 70 ℃ | 95.1 | 95.2 | 94.4 | |
| Averaged particles footpath (nm) | After just having made | 52.3 | 46.4 | 49.6 |
| Preserved 7 days for 70 ℃ | 49.2 | 49.6 | 50.7 | |
| Organoleptic test's (taste and take sense) | ○ | ○ | ○ | |
As known from Table 4, can obtain and the irrelevant supernatant liquid of transmitance more than 90% of the concentration of glycerol.In addition, even this diluent was preserved 7 days at 70 ℃, transmitance and averaged particles footpath almost do not change yet.
Embodiment 20-22
Use acetic acid d-alpha-tocopherol as liposoluble substance, according to prescription shown in the table 5, with each component with simple blender (90rpm), 85 ± 5 ℃ heat be stirred to preparation and clarify after, be cooled to room temperature, obtain soluble liquide preparation.With this liquor at 5 ℃, 45 ℃,-10 ℃/40 ℃ (12 hours heating and cooling times, 48 hours periods of each temperature retention time 12) preserved 2 months, or 45 ℃ preserve 2 months after, add purified water and make the soluble liquide preparation diluent of acetic acid d-alpha-tocopherol content 100mg, carry out transmitance according to the same quadrat method of embodiment 1-8 and measure.Its result is as shown in table 5.From this result as can be known, identical with initial value after the firm manufacturing, also can obtain the supernatant liquid of transmitance more than 90% after the preservation, can confirm that this soluble liquide preparation has good stability.
In addition, this soluble liquide preparation is added aforementioned commercially available oral liquid (A) 100mL or commercially available oral liquid (B) 100mL (contains taurine 1000mg among 1 bottle of 100mL, inositol 50mg, nicotiamide 20mg, vitamin b1 nitrate 5mg, vitamin B
2Phosphate ester 5mg, vitamin B
65mg, Caffeine Anhydrous 50mg) in, making the content of acetic acid d-alpha-tocopherol in per 1 bottle is 100mg, obtains the soluble liquide preparation diluent.These diluents are measured transmitance according to the same quadrat method of embodiment 1-8, check taste and take sense.The result is as shown in table 5.From this result as can be known, comparing taste with the commercially available product of not adding soluble liquide preparation and taking sense does not have difference, is good.In addition, diluent 70 ℃ of transmitances after preserving 1 day and 7 days, not being had significant change with transmitance after the firm manufacturing, is clarifying liquid.
Table 5
| Implementation column | |||||||
| 20 | 21 | 22 | |||||
| Prescription (%) | Acetic acid-d-alpha-tocopherol | 10 | 10 | 10 | |||
| SY-Glyster MSW 750 | 5 | 5 | 5 | ||||
| Polyoxyethylene hardened castor oil 60 | 8.5 | 8.5 | 8.5 | ||||
| Glycerol | 51.0 | 52.5 | 55.0 | ||||
| Purified water | 25.5 | 24 | 21.5 | ||||
| Add up to | 100 | 100 | 100 | ||||
| Preserve back transmitance (%) | After just having made | 96.6 | 97.9 | 97.8 | |||
| Cyclic test 2 months | 96.1 | 96.1 | 97.5 | ||||
| Preserved 2 months for 45 ℃ | 94.8 | 97.6 | 97.9 | ||||
| The transmitance of diluent (%) | (A) *1 | (B) *2 | (A) *1 | (B) *2 | (A) *1 | (B) *2 | |
| After just having made | 97.1 | 97.5 | 98.0 | 97.2 | 98.0 | 98.3 | |
| Preserved 1 day for 70 ℃ | 97.1 | 97.5 | 98.1 | 98.0 | 97.4 | 98.0 | |
| Preserved 7 days for 70 ℃ | 94.1 | 95.4 | 95.2 | 95.6 | 94.3 | 95.9 | |
| Organoleptic test's (taste and take sense) | ○ | ○ | ○ | ○ | ○ | ○ | |
* 1: with commercially available product oral liquid (A) dilution
* 2: with commercially available product oral liquid (B) dilution
Embodiment 23
According to the prescription of table 6, in the purified water of 80 weight % (about 80 ℃), dissolving is to behind hydroxyl methyl formate and the sodium benzoate, and adding Polyethylene Glycol (PEG4000), powder reduction maltose syrups, glycerol stir, and are cooled to room temperature and obtain clarifying liquid.Further add the soluble liquide preparation and the purified water (surplus) of L-arginine and vitamin C derivatives, embodiment 21 preparations, be stirred to the supernatant liquid that obtains homogeneous, obtain containing vitamin E and ascorbic astringent.This astringent is the supernatant liquid of transmitance 97.1%, and pH is 4.7.Usability is fine, and sensation is not sticking, is salubrious.
In addition, make astringent after similarly the soluble liquide preparation of embodiment 21 being added with 0.5,3 or 5%, also sticking, be to use the salubrious lotion of sense.
Embodiment 24
According to the prescription of table 6, in the purified water of 80 weight % (about 80 ℃), dissolving is slowly added carboxy vinyl polymer to behind hydroxyl methyl formate, sodium benzoate, episilon amino caproic acid, the glycerol, stirs, and obtains the dispersion liquid of homogeneous.This dispersion liquid is cooled to about 50 ℃, under agitation adds triethanolamine aqueous solution (5% purified water in the prescription), obtain clarifying gel.Further add embodiment 21 synthetic soluble liquide preparations and purified water (remainder), be stirred to homogeneous, obtain containing the gel of vitamin E.This gel usability is not sticking, very salubrious.
In addition, the gel that makes after similarly the soluble liquide preparation of embodiment 21 being added with 0.5,3 or 5% does not rely on concentration, and usability is sticking, very salubrious.
Table 6
| Embodiment 23 (lotion) | Embodiment 24 (gel) | ||
| Prescription (%) | The soluble liquide preparation of embodiment 21 | 1.0 | 1.0 |
| Ascorbic acid glucoside | 2.0 | - | |
| The Gentiana extract | 2.0 | - | |
| Episilon amino caproic acid | - | 0.1 | |
| Glycerol | 1.0 | 2.0 | |
| The powder reduction maltose syrups | 2.0 | - | |
| PEG4000 | 1.5 | - | |
| Methyl parahydroxybenzoate | 0.05 | 0.15 | |
| Sodium benzoate | 0.3 | 0.3 | |
| The L-arginine | 1.0 | - | |
| Carboxy vinyl polymer | - | 0.4 | |
| Triethanolamine | - | 0.3 | |
| Purified water | In right amount | In right amount | |
| Add up to | 100.0 | 100.0 | |
Embodiment 25-26
According to the prescription of table 7, in the purified water of 80 weight % (about 80 ℃), dissolving adds PEG4000 to behind hydroxyl methyl formate, sodium benzoate, the xanthan gum, and xylitol, glycerol stir, and are cooled to room temperature and obtain clarifying liquid.Further add L-arginine and vitamin C derivatives, embodiment 21 synthetic soluble liquide preparations are stirred to the supernatant liquid that obtains homogeneous, obtain containing vitamin E and ascorbic astringent.These lotions were preserved 2 months under cooling condition, or preserved 2 months according to same cycle of the cyclic test of embodiment 20-22, or preserved 2 months, its character is estimated at 45 ℃.Its result no matter initial pH how, is stable, does not have the variation of character (clarification property, abnormal smells from the patient).Usability is not sticking yet, feels good.
Table 7
| Embodiment 25 | Embodiment 26 | ||
| Prescription (%) | The soluble liquide preparation of embodiment 21 | 1.0 | 1.0 |
| Ascorbic acid glucoside | 2.0 | 2.0 | |
| Glycerol | 2.5 | 2.5 | |
| Xylitol | 2.0 | 2.0 | |
| PEG4000 | 1.5 | 1.5 | |
| Methyl parahydroxybenzoate | 0.05 | 0.05 | |
| Sodium benzoate | 0.3 | 0.3 | |
| The L-arginine | 1.0 | 1.5 | |
| Xanthan gum | 0.2 | 0.2 | |
| Purified water | In right amount | In right amount | |
| Add up to | 100.0 | 100.0 | |
| Character | After just having made | Light yellow transparent | Light yellow transparent |
| Cooling preservation 2 months | Light yellow transparent | Light yellow transparent | |
| Cyclic test 2 months | Light yellow transparent | Light yellow transparent | |
| Preserved 2 months for 45 ℃ | Light yellow transparent | Light yellow transparent | |
| PH | 5.8 | 8.7 | |
Claims (10)
1, the soluble liquide preparation compositions of liposoluble substance, contain and be selected from the vitamin E class, retinoid, beta-carotene, the vitamin D class, the vitamin K class, crotamiton, teprenone, indometacin, the liposoluble substance of prednisolone and tannic acid and (1) are with respect to more than the liposoluble substance 50 weight %, what be less than 100 weight % is selected from least a of polyoxyethylene hardened castor oil and polyoxyethylene castor oil, (2) with respect to the polyglyceryl fatty acid ester that is selected from of liposoluble substance 5-100 weight %, polyoxyethylene sorbitan fatty acid ester, the polyoxyethylene fatty acid glyceride, sucrose fatty acid ester and polyoxyethylene alkyl ether at least a, (3) with respect to the glycerol that is selected from of soluble liquide preparation total amount 10-80 weight %, diglycerol, two triglycerols, polyglycereol, propylene glycol, dipropylene glycol, 1,3 butylene glycol, ethylene glycol, Polyethylene Glycol, Sorbitol, the polyhydric alcohol of mannitol and xylitol.
2, the compositions of claim 1 record, the amount of liposoluble substance is 3-15 weight % with respect to the full dose of soluble liquide preparation.
3, the compositions of claim 1 record, liposoluble substance is the vitamin E class.
4, the compositions of claim 3 record, the vitamin E class is to be selected from the dl-alpha-tocopherol, the d-alpha-tocopherol, acetic acid dl-alpha-tocopherol, acetic acid d-alpha-tocopherol, succinic acid dl-alpha-tocopherol, succinic acid d-alpha-tocopherol, nicotinic acid dl-alpha-tocopherol, nicotinic acid d-alpha-tocopherol, the dl-betatocopherol, the d-betatocopherol, acetic acid dl-betatocopherol, acetic acid d-betatocopherol, succinic acid dl-betatocopherol, succinic acid d-betatocopherol, nicotinic acid dl-betatocopherol, nicotinic acid d-betatocopherol, the dl-Gamma-Tocopherol, the d-Gamma-Tocopherol, acetic acid dl-Gamma-Tocopherol, acetic acid d-Gamma-Tocopherol, succinic acid dl-Gamma-Tocopherol, succinic acid d-Gamma-Tocopherol, nicotinic acid dl-Gamma-Tocopherol, nicotinic acid d-Gamma-Tocopherol, the dl-Delta-Tocopherol, the d-Delta-Tocopherol, acetic acid dl-Delta-Tocopherol, acetic acid d-Delta-Tocopherol, succinic acid dl-Delta-Tocopherol, succinic acid d-Delta-Tocopherol, nicotinic acid dl-Delta-Tocopherol, nicotinic acid d-Delta-Tocopherol and tocotrienol at least a.
5, the compositions of claim 3 record, the vitamin E class is an acetic acid d-alpha-tocopherol.
6, the diluent of soluble liquide preparation compositions, the soluble liquide preparation compositions of claim 1 record is diluted with purified water, buffer or aqueous liquor, full dose with respect to the diluent of soluble liquide preparation compositions contains liposoluble substance 0.001-0.5 weight %.
7, the diluent of soluble liquide preparation compositions, with purified water, buffer or the dilution of aqueous liquor, the full dose with respect to the diluent of soluble liquide preparation compositions contains liposoluble substance 0.01-0.3 weight % with the soluble liquide preparation compositions of claim 1 record.
8, the manufacture method of the soluble liquide preparation compositions of liposoluble substance, it is characterized in that being selected from the vitamin E class, retinoid, beta-carotene, the vitamin D class, the vitamin K class, crotamiton, teprenone, indometacin, mix (1) in the liposoluble substance of prednisolone and tannic acid with respect to more than the liposoluble substance 50 weight %, what be less than 100 weight % is selected from least a of polyoxyethylene hardened castor oil and polyoxyethylene castor oil, (2) with respect to the polyglyceryl fatty acid ester that is selected from of liposoluble substance 5-100 weight %, polyoxyethylene sorbitan fatty acid ester, the polyoxyethylene fatty acid glyceride, sucrose fatty acid ester and polyoxyethylene alkyl ether at least a, further mix (3) glycerol that is selected from respect to soluble liquide preparation total amount 10-80 weight %, diglycerol, two triglycerols, polyglycereol, propylene glycol, dipropylene glycol, 1,3 butylene glycol, ethylene glycol, Polyethylene Glycol, Sorbitol, the polyhydric alcohol of mannitol and xylitol.
9, the method for claim 8 record, wherein liposoluble substance is the vitamin E class.
10, the method for claim 8 or 9 records, to in liposoluble substance, mix (1) and be selected from least a of polyoxyethylene hardened castor oil and polyoxyethylene castor oil, (2) be selected from least a of polyglyceryl fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid glyceride, sucrose fatty acid ester and polyoxyethylene alkyl ether, further mix (3) polyhydric alcohol mixture afterwards, carry out 100～5000kg/cm
2Pressure handle down.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000203394 | 2000-07-05 | ||
| JP203394/2000 | 2000-07-05 |
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|---|---|---|---|
| CNB011259159A Expired - Fee Related CN1180767C (en) | 2000-07-05 | 2001-07-05 | Soluble liquide preparation of liposoluble matter |
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| Country | Link |
|---|---|
| KR (1) | KR100722326B1 (en) |
| CN (1) | CN1180767C (en) |
| TW (1) | TWI254637B (en) |
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| KR100953241B1 (en) | 2003-10-10 | 2010-04-16 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | Novel Liquid Preparation Composition |
| KR100718279B1 (en) * | 2004-11-10 | 2007-05-16 | 한국콜마 주식회사 | Clear liquid formulation containing hedera extract |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JPS615011A (en) * | 1984-06-18 | 1986-01-10 | Ss Pharmaceut Co Ltd | Stable vitamin e solubilized solution |
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2001
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- 2001-07-04 TW TW090116354A patent/TWI254637B/en not_active IP Right Cessation
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| KR20020003509A (en) | 2002-01-12 |
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