GB2147263A - Compositions for making vesicles - Google Patents
Compositions for making vesicles Download PDFInfo
- Publication number
- GB2147263A GB2147263A GB08422628A GB8422628A GB2147263A GB 2147263 A GB2147263 A GB 2147263A GB 08422628 A GB08422628 A GB 08422628A GB 8422628 A GB8422628 A GB 8422628A GB 2147263 A GB2147263 A GB 2147263A
- Authority
- GB
- United Kingdom
- Prior art keywords
- group
- carbon atoms
- hydrocarbon
- ion
- vesicles
- 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
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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
- A61K9/1272—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Biophysics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Manufacturing Of Micro-Capsules (AREA)
- Emulsifying, Dispersing, Foam-Producing Or Wetting Agents (AREA)
Abstract
Vesicular compositions comprise the ingredients: (A) a quaternary ammonium salt of the formula (I> <IMAGE> in which R1 and R2 are respectively a C10-C24 hydrocarbon group, R3 and R4 are respectively a C1-C4 hydrocarbon or hydroxyhydrocarbon group or a benzyl group, and X(-) is an anion; and (B) one or more surface active agents selected from the specific groups.
Description
SPECIFICATION
Compositions for vesticles
i) Field of the invention
This invention relates to compositions for vesicles and more particularly, to compositions for vesicles which are able to form stable vesicles over a long term.
ii) Description of the prior art
It is well known that phospholipids and particularly lecithin, which are important constituents of biomembrane, form in water double-layered hollow vesicles called liposome. This liposome is a hollow lipid double-layered sphere and can contain various chemical substances in the lumen thereof and thus has a close resemblance with red cells with regard to the structure. In this sense, the liposome has been studied as a model of red cell or a cellular model and plays an important role in the studies of biomembranes.
in recent years, attention has been paid to the liposome as a carrier in vivo of drugs. More particularly, the liposome which is able to contain various chemical substances in the lumen thereof may be regarded as a kind of capsule. It has been reported that when a drug is dosed after included in the liposome, the metabolism in vivo of the drug is suppressed and the drug is kept in the living body over a long term, sustaining its medical efficacy (see, for example, FEBS Letters, Vol. 36, No. 3, page 292, 1973), side effects of drugs, e.g. allergy, are suppressed (see, for example, FEBS Letters, Vol.45, No. 1, page 71, 1974), and distribution of drug into various organs changes (see, for example, Eur. J. Biochem. Vol. 47, page 179, 1974).
As noted above, liposome exhibits good properties as a carrier in vivo of drug and particularly, its property of changing the distribution of drug into organs has the possibility of enabling a drug to be selectively acted on affected organs, attracting the attention as the so-called target effect with liposome. For instance, most anticancer drugs involve side effects because they act not only on cancer cells, but also on healthy normal cells. If it is possible that an anticancer drug is selectively acted on cancerous cells by administering it after incorporation into liposome, this mode of administration is considered to be very useful. In practice, such attempts give good results in some cases (for example, Collection of Summaries of Lectures to the Meeting of the Japanese Cancer Society, page 8, (1976)).
On the other hand, a suitable conductive material such as alkylamine is embedded in the double-layered portion while placing a photoreductive substance such as cupric ions into the internal liquid of the liposome and a photooxidative substance such as ascorbic acid into the external liquid of the liposome. Subsequently, when such liposome is irradiated with light, it becomes possible to condense a specific type of ion from the external to internal liquids depending on the property of the conductive material embedded in the double-layered membrane. For instance, it is possible to collect, as resources, specific types of elemental ions from sea water.
As noted above, liposome will bring about an epoch-making, new technique such as in administration of drugs. However, because phospholipids capable of forming the liposome are living body-derived substances, there are great limitations on their chemical structures, so that there are disadvantages such as inconvenience in imparting various functions thereto and relatively poor chemical stability.
In order to eliminate such limitations on the phospholipid liposome, studies have been recently made to form liposome-type vesicles from synthetic surface active agents. It has been confirmed at present that several kinds of surface active agents have the ability of forming vesicles. Such vesicles of surface active agents have the double-layered hollow vesicular structure similar to liposome and can thus be applicable as a carrier for drug as noted before.
However, known vesicles of surface active agents are all prepared by dispersing surface active agents in water and irradiating the dispersion, for example, with ultrasonic wave. Because the resulting vesicular structure is unstable, the vesicles cannot be preserved over a long term. More particularly, where dialkyldimethylammonium salts used in the present invention are used to obtain vesicles according to the above-described known method, the vesicular structure is broken within several days with the vesicle solution becoming turbid or gelled.
For utilization of the surface active agent vesicles as the drug carrier or for other purposes, it seems essential to improve the stability and thus there is a strong demand of developing techniques for the improvement.
Summary ofthe invention
In view of the above circumstance, the present inventors have made intensive studies to obtain vesicles stable over a long term and, as a result, found that vesicles obtained from a system of a specific type of quaternary ammonium salt having the ability of forming vesicles, a kind of surface active agent and water is stable over a long term. The present invention is accomplished on the basis of the above finding.
Accordingly, an object of this invention is to provide a composition for vesicles which comprises the following two ingredients (A) and (B), the ratio by weight of (A) and (B) ingredients being in the range of 100:1 to 100:100, (A) a two-chain type quaternary ammonium salt of the general formula (I)
TAKE IN HERE 1
in which
R1 and R2: hydrocarbon group having from 10 to 24 carbon atoms,
R3 and R4: hydrocarbon or hydroxyhydrocarbon group having from 1 to 4 carbon atoms, or benzyl group, and XO: anion serving as a counter ion of the quaternary ammonium ion,
(B) one or more surface active agents selected from the group consisting of compounds of the formulas (a)
TAKE IN HERE 2
R6O(AO)nH (b)
TAKE IN HERE 3
HO(AO)p(C3H6O)q(AO)rH (d)
TAKE IN HERE 4
R6COO(AO)nR,o (9)
(AO)mH R6N
(AO)nH (k)
AOH (I R6CON (I) AOH
in which, Rg: hydrocarbon or hydroxyhydrocarbon group having from 1 to 4 carbon atoms, or benzyl group,
R6: hydrocarbon group having from 8 to 36 carbon atoms,
R7: hydrocarbon group having from 5 to 23 carbon atoms,
Rs, Rg and R10: hydrogen atom or acyl group having from 6 to 24 carbon atoms (provided that when both
R7 and R8 are contained in one molecule, at least one of them is hydrogen atom),
R11 and R12: hydrogen atom or hydrocarbon group having from 6 to 24 carbon atoms (provided that at least one of them is hydrogen atom),
R,3: hydrocarbon group having from 9 to 23 carbon atoms,
R14: hydrocarbon or hydroxyhydrocarbon group having from 1 to 24 carbon atoms, or benzyl group,
R15, R16 and R17: hydrocarbon group having from 1 to 24 carbon atoms,
A: alkylene group having from 2 to 4 carbon atoms,
M: alkali metal ion, monoethanolammonium ion, diethanolammonium ion ortriethanolammonium ion,
I, m and n: O or an integer of from 1 to 150,
p, q and r: integer of from 1 to 150,
t: integer of from 1 to 4.
same same meaning as defined before.
It has been already known that the two-chain type quaternary ammonium salts, which are (A) ingredient, from vesicles as disclosed in Japanese Laid-open Patent Application No. 53-134784 and reported in J. Am.
Chem. Soc., Vol. 99, page 3860 (1977) and J. Colloid Interface Sci., Vol.65, No. 1, page 155(1978) and J. Am.
Chem. Soc., Vol. 101, page 4030 (1979). However, it is not known that the vesicles are kept stable over a long term by incorporating (B) ingredient into (A) ingredient. This has been uncovered for the first time by the present inventors.
Detailed description of the invention and preferred embodiments
Examples of (A) ingredient of the present invention include didecyldimethylammonium salt, didodecyldimethyl-ammonium salt, ditetradecyldimethylammonium salt, dihexadecyldimethylammonium salt, dioctadecyldimethylammonium salt, dieicosyldimethylammonium salt, didecyl-N-hydroxyethyl-Nmethylammonium salt, dodecyl-N-hydroxyethyl-N-methylammonium salt, ditetradecyl-N-hydroxyethyl-Nmethylammonium salt, dihexadecyl-N-hydroxyethyl-N-methylam monium salt, dioctadecyl-N-hydroxyethyl
N-methylammonium salt, dieicosyl-N-hydroxyethyl-N-methylammonium salt, and the like. With regard to counter ions of (A) ingredient, they are not critical but are preferred to be halogen ions, methylsulfate ions, and ethylsulfate ions.
The surface active agents which are used as (B) ingredient in the practice of the invention are considered to have the action of stabilizing vesicles. The surface active agent enumerated in (a) is a cationic active agent, those agents of (b) through (m) are nonionic active agents, and those agents of (n) through (q) are amphoteric active agents. In these (B) ingredients, the alkylene oxide added to the nonionic active agents of (b) through (m) is preferably ethylene oxide.
In the composition for vesicles of the invention, the mixing ratio by weight of (A) and (B) ingredients is important and should be in the range offrom 100:1 to 100:100. Outside the above range, no vesicles are formed, or even if vesicles are formed, they are unstable.
For the preparation of the vesicular composition according to the invention, (A) and (B) ingredients are dissolved in solvents capable of dissolving both ingredients, followed by agitating to obtain a uniform solution and removing the solvent therefrom according to any known procedures.
In order to obtain vesicles from the thus obtained composition of the invention, it is sufficient to suspend the vesicular composition in water and subject the suspension to ultrasonic irradiation. Aside from the above procedure, vesicle solutions may be obtained, for example, by a procedure in which the vesicular composition is dissolved in a solvent miscible in water such as ethanol and the solution is intensely injected into water, or by a procedure in which the vesicular composition is solubilized with water-soluble surface active agents and subjected to dialysis to remove the surface active agent.
The vesicle solution prepared from the vesicular composition of the invention should preferably have a concentration of from 1 to 50 wt% (hereinafter referred to simply as %), more preferably from 5 to 30%.
When the concentration exceeds 50%, its viscosity becomes too high, which may cause disadvantages in the preparation and use of vesicles. In case where the concentration is less than 1%, no troubles in the preparation and use take place but the costs of transportation of and container for the vesicle solution increase, thus being not economical.
The most reliable method, currently known in the art, of confirming vesicles in the thus prepared vesicle solution is electron-microscopic observation using a negative staining technique. The negative staining technique is a method in which the electron density of the hydrophilic moieties of surface active agents capable of forming vesicles is increased by means of phosphotungstic acid or uranyl acetate and the moieties are stained black. In the practice of the invention, formation of vesicles was observed through the microscopic observation. The vesicle solution containing vesicles are transparent with good fluidity. On the other hand, the solution in which the compounds used do not form vesicles but give a multi-layered structure is gelled and opaque with very poor fluidity.Accordingly, in the stability test of vesicles (described hereinafter in detail), it is possible to judge the stability of a vesicular composition by preparing a vesicle solution by the ultrasonic method and observing transparency and fluidity of the solution as a function of time. One of supplementary simple methods of confirming vesicles is a NMR method. The relaxation time or width of absorption line of 1 H - or 13C- NMR of vesicles is largely different from that of cases other than vesicles. More particularly, with vesicles, the relaxation time is prolonged with a narrow, sharp width of absorption line. In cases other than vesicles, the relaxation time is short with a large width of absorption line.
However, the presence of the double-layered structure by which vesicles are characterized cannot be directly confirmed by the NMR method. In order to strictly confirm the presence of vesicles, the observation through an electron microscope must be made.
The present invention is illustrated in more detail by way of examples, which should not be construed as limiting the present invention.
Example 1
Vesicular compositions were prepared from two-chain type quaternary ammonium salts and various surface active agents indicated in Table 1 to check formation and stability of the resulting vesicles.
JPreparation of compositions for vesicles
Ten grams of a respective two-chain type quaternary ammonium salt dissolved in chloroform and 1 g of each surface agent were mixed and agitated until a uniform solution was obtained. Subsequently, the chloroform was removed using an evaporator to obtain a powder of the vesicular composition.
Formation and confirmation ofvesicles] Ten grams of the resulting composition in the form of powder was admixed with 90 g of water, followed by agitating to obtain a viscous, opaque gel-like composition. The gel-like composition was kept at 60"C and subjected to ultrasonic irradiation at 100W and 25 KHz for about 1 hour. The resulting solution was observed through an electron microscope by which formation of vesicles was confirmed. It will be noted that solutions in which vesicles were formed were substantially transparent and fluid.
[Stability test of vesicles]
The vesicle solutions thus obtained were preserved for 3 months in a thermostatic chamber of 20 C. The stability was evaluated by comparing the state of each solution after 3 months with the state thereof immediately after the preparation with regard to transparency and fluidity. The evaluation standards for the formation and stability of vesicles are as follows.
A: The state after the preservation is completely same as the state immediately after the preparation with the vesicular structure being perfectly kept.
B: As compared with the solution immediately after the preparation, only a slight increase of viscosity is recognized with the vesicular structure being substantially perfectly kept.
C: The solution increases in viscosity and is considerable in opacity with little vesicular structure existing.
D: The solution immediately after the preparation becomes completely gelled and opaque with no vesicular structure being recognized.
*: Even through the ultrasonic irradiation is effected, no vesicles are formed.
TABLE 1
Results of Observation
Surface Surface Surface Surface
Active Active Active Active
Agent* Agent 1 Agent2 Agent3
Two-chain Type
QuaternaryAmmonium Salt
Didecyldimethylammonium
chloride B B B
Didoceyldimethylammonium
chloride A B B Ditetradecyldimethylammonium chloride A B A
Dihexadecyldimethylammonium
chloride A B A
Dioctadecyldimethylammonium
chloride A B A
Dieicocyldimethylammonium
chloride B B A
Didecyl-N-hydroxyethyl-N
methylammonium chloride B B B
Didodecyl-N-hydroxyethyl-N
methylammonium chloride B B B
Ditetradecyl-N-hydroxyethyl
N-methylammonium chloride A A A
Dihexadecyl-N-hydroxyethyl
N-methylammonium chloride A A A
Dioctadecyl-N-hyd roxyethyl
N-methylammonium chloride A A A
Dieicosyl-N-hydroxyethyl-N
methylammonium chloride A B A
Didecyl-N-benzyl-N
methylammonium chloride B B B
TABLE 1 (Cont'd)
Results of Observation
Surface Surface Surface Surface
Active Active Active Active
Agent* Agent 1 Agent2 Agent3
Two-chain Type
QuaternaryAmmonium Salt
Didodecyl-N-benzyl-N
methylammonium chloride B B B Ditetradecyl-N-benzyl-N- methylammonium chloride B A A
Dihexadecyl-N-benzyl-N
methylammonium chloride B A A
Dioctadecyl-N-benzyl-N
methylammonium chloride B A A
Dieicosyl-N-benzyl-N
methylammonium chloride B B A
Dioleyldimethylammonium
chloride A B A Dioleyl-N-hydroxyeth yl-N- methylammonium chloride A B A
Dioleyl-N-benzyl-N
methylammonium chloride A B A * Surface active agents
Surface active agent 1
(N,N-dipolyoxyethylene-N-stearylamine, m + n = 20)
Surface active agent2
(trimethylstearylammonium chloride)
Surface active agent3
(distearylaminimide)
Comparative Example 1
Ten grams of each of the two-chain type quaternary ammonium salts indicated in Table 1 was dissolved in 90 g of water, followed by forming vesicles according to the procedure of Example 1. The vesicle solutions were preserved in a thermostatic chamber of 20"C for 3 months to check the state thereof after the preservation. In all cases using the 21 quaternary ammonium salts, vesicles were found to be formed, but after the preservation of 3 months, the solutions became gelled and opaque with a loss of the vesicular structure.
Example 2
Dioctadecyldimethylammonium chloride and the surface active agents indicated in Table 2 were used to prepare compositions for vesicles according to the procedure of Example 1. The stability of vesicles obtained from the compositions was determined. The results are shown in Table 2.
TABLE 2
Results of
Surface Active Agent Observation
Trimethylstearylammonium chloride B
Stearyl alcohol A
Polyoxyethylene stearyl ether (n = 100) A
Polyoxyethylene nonylphenyl ether (n = 10) B
Polyoxyethylene polyoxypropylene block
polymer (p = 10, q = 10, r = 10) A
Polyoxyethylene sorbitan stearate
(I + m + n = 5) B
Sorbitan stearate B Pentaervthritol stearate A
Polyoxyethylene stearate (n = 7) A
Stearyl gylceryl ether A
Stearic acid monoglyceride A
Polyoxyethylene glycerine stearate (I + m + n =8) A
Polyoxyethylene stearyl amine
(m + n = 20) A
Stearic acid diethanolamide A
Stearyldimethylamine oxide B
Distearylaminimide A
Stearyl dimethylcarbobetaine (t = 1) B
Sodium dodecylaminocarboxylate (t = 1) B
Stearyldimethylsulfobetaine (t = 3) B
Example 3
Twelve chain type quaternary ammonium salts in total indicated in Table 3 and the three surface active agents used in Example 1 were used in combination to prepare 36 vesicular compositions according to the procedure of Example 1 in order to check the stability of vesicles obtained from the respective compositions
The results are shown in Table 3.
TABLE 3
Results of Observation
Surface Surface Surface Surface
Active Active Active Active
Agent* Agent 1 Agent2 Agent3
Two-chain Type Ouaternary A mmonium Salt
Dioctadecyldimethylammonium
bromide A B A
Dioctadecyldimethylammonium
methyl-sulfate B A A
Dioctadecyldimethylammonium
ethylsulfate B B B
Dioctadecyldimethylammonium
acetate B B B
Dioctadecyl-N-hydroxyethyl
N-methylammonium bromide A B A
Dioctadecyl-N-hydroxyethyl
N-methylammonium methylsulfate B B A
Dioctadecyl-N-hydroxyethyl
N-methylammonium ethylsulfate B A A
Dioctadecyl-N-hydroxyethyl
N-methylammonium acetate B B B
Dioctadecyl-N-benzyl-N
methylammonium bromide B B A
Dioctadecyl-N-benzyl-N
methylammonium methylsulfate B B A
Dioctadecyl-N-benzyl-N
methylammonium ethylsulfate B B A
Dioctadecyl-N-benzyl-N
methylammonium acetate B B B
Example 4
Dioctadecyldimethylammonium chloride and the surface active agents used in Example 1 were mixed in different rations indicated in Table 4, followed by preparing 39 vesicular compositions in total according to the procedure of Example 1. The compositions were used to determine their formation and stability of vesicles. The results are shown in Table 4.
TABLE 4
Results of Observation
Surface
Active
Mixing Ratio Agent (by weight) Surface Surface Surface
Active Active Active
Dioctadecylammonium Agent 1 Agent2 Agent3
Chloride
Surface Active
Agent
100/0.5 C C C
100/1.0 B B B
100/1.1 B B B
10011.25 B B B
100/1.67 B B A
100/2.0 A B A
100/2.5 A B A
100/5.0 A B A
100/10 A B A
100/20 A B A
100150 A B B
100/100 B B B
100/200 * * C
Claims (4)
1. A composition for vesicles comprising the following two ingredients (A) and (B), the ratio of (A) ingredient to (B) ingedient ranging from 100:1 to 100:100,
(A) a two-chain type quaternary ammonium salt of the general formula (I)
in which
R1 and R2: hydrocarbon group having from 10 to 24 carbon atoms,
R3 and R4: hydrocarbon or hydroxyhydrocarbon group having from 1 to 4 carbon atoms, or benzyl group, and X: anion serving as a counter ion of the quaternary ammonium ion,
(B) one or more surface active agents selected from the group consisting of compounds of the formulas (a) to (q),
R6O(AO)nH (b)
HO(AO)p(C3H6O)q(AO)rH (d)
R6COO(AO)nR1o (9)
AOH R6CON (I)
AOH
R15NH(A)tCOOM (p)
in which,
R5: hydrocarbon or hydroxyhydrocarbon group having from 1 to 4 atoms, or benzyl group,
R6: hydrocarbon group having from 8 to 36 carbon atoms,
R7: hydrocarbon group having from 5 to 23 carbon atoms,
R8, Rg and R10: hydrocarbon atom or acyl group having from 6 to 24 carbon atoms (provided that when both R7 and R8 are contained in one molecule, at least one of them is hydrogen atom),
R11 and R12: hydrocarbon atom or hydrocarbon group having from 6 to 24 carbon atoms (provided that at least one of them is hydrogen atom),
R13: hydrocarbon group having from 9 to 23 carbon atoms,
R14: hydrocarbon or hydroxyhydrocarbon group having from 1 to 24 carbon atoms, or benzyl group,
R15, R16 and R17: hydrocarbon group having from 1 to 24 carbon atoms,
A: alkylene group having from 2 to 4 carbon atoms,
M: alkali metal ion, monoethanolammonium ion, diethanolammonium ion ortriethanolammonium ion,
I, m and n: Koran integer of from 1 to 150,
p, q and r: integer of from 1 to 150,
t: integer of from 1 to 4.
XO: same meaning as defined before.
2. The composition according to Claim 1, wherein the counter ion XO in each of ingredients (A) and (B) is halogen ion, methylsulfate ion or ethylsulfate ion.
3. A composition as claimed in claim 1 and substantially as described in any one of the specific examples hereinbefore set forth.
4. Each and every novel embodiment herein set forth either separately or in combination.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP58181629A JPS6072831A (en) | 1983-09-29 | 1983-09-29 | Composition for vesicle |
Publications (3)
Publication Number | Publication Date |
---|---|
GB8422628D0 GB8422628D0 (en) | 1984-10-10 |
GB2147263A true GB2147263A (en) | 1985-05-09 |
GB2147263B GB2147263B (en) | 1987-03-25 |
Family
ID=16104113
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB08422628A Expired GB2147263B (en) | 1983-09-29 | 1984-09-07 | Compositions for making vesticles |
Country Status (4)
Country | Link |
---|---|
JP (1) | JPS6072831A (en) |
DE (1) | DE3435516A1 (en) |
FR (1) | FR2552679B1 (en) |
GB (1) | GB2147263B (en) |
Cited By (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1989000812A1 (en) * | 1987-07-28 | 1989-02-09 | Micro-Pak, Inc. | Method of manufacturing unilamellar lipid vesicles |
US4855090A (en) * | 1987-03-13 | 1989-08-08 | Micro-Pak, Inc. | Method of producing high aqueous volume multilamellar vesicles |
US4911928A (en) * | 1987-03-13 | 1990-03-27 | Micro-Pak, Inc. | Paucilamellar lipid vesicles |
US4917951A (en) * | 1987-07-28 | 1990-04-17 | Micro-Pak, Inc. | Lipid vesicles formed of surfactants and steroids |
US4942038A (en) * | 1987-03-13 | 1990-07-17 | Micro Vesicular Systems, Inc. | Encapsulated humectant |
US5000960A (en) * | 1987-03-13 | 1991-03-19 | Micro-Pak, Inc. | Protein coupling to lipid vesicles |
WO1991004012A1 (en) * | 1989-09-21 | 1991-04-04 | Micro Vesicular Systems, Inc. | Paucilamellar lipid vesicles using charge-localized, single chain, nonphospholipid surfactants |
US5019174A (en) * | 1988-03-03 | 1991-05-28 | Micro Vesicular Systems, Inc. | Removing oil from surfaces with liposomal cleaner |
US5019392A (en) * | 1988-03-03 | 1991-05-28 | Micro-Pak, Inc. | Encapsulation of parasiticides |
US5023086A (en) * | 1987-03-13 | 1991-06-11 | Micro-Pak, Inc. | Encapsulated ionophore growth factors |
US5104736A (en) * | 1988-03-03 | 1992-04-14 | Micro-Pak, Inc. | Reinforced paucilamellar lipid vesicles |
US5160669A (en) * | 1988-03-03 | 1992-11-03 | Micro Vesicular Systems, Inc. | Method of making oil filled paucilamellar lipid vesicles |
US5164191A (en) * | 1991-02-12 | 1992-11-17 | Micro Vesicular Systems, Inc. | Lipid vesicles having an alkyd as a wall-forming material |
US5213805A (en) * | 1991-07-25 | 1993-05-25 | Micro Vesicular Systems, Inc. | Lipid vesicles having n,n-dimethylamide derivatives as their primary lipid |
US5234767A (en) * | 1987-03-13 | 1993-08-10 | Micro-Pak, Inc. | Hybrid paucilamellar lipid vesicles |
US5260065A (en) * | 1991-09-17 | 1993-11-09 | Micro Vesicular Systems, Inc. | Blended lipid vesicles |
US5405615A (en) * | 1991-09-17 | 1995-04-11 | Micro Vesicular Systems, Inc. | Sucrose distearate lipid vesicles |
US5439967A (en) * | 1991-09-17 | 1995-08-08 | Micro Vesicular Systems, Inc. | Propylene glycol stearate vesicles |
WO1996010390A1 (en) * | 1994-09-30 | 1996-04-11 | Inex Pharmaceuticals Corp. | Novel compositions for the introduction of polyanionic materials into cells |
US5628936A (en) * | 1987-03-13 | 1997-05-13 | Micro-Pak, Inc. | Hybrid paucilamellar lipid vesicles |
US5643600A (en) * | 1991-09-17 | 1997-07-01 | Micro-Pak, Inc. | Lipid vesicles containing avocado oil unsaponifiables |
US5785992A (en) * | 1994-09-30 | 1998-07-28 | Inex Pharmaceuticals Corp. | Compositions for the introduction of polyanionic materials into cells |
US7749520B2 (en) | 2004-07-07 | 2010-07-06 | Statens Serum Institut | Compositions and methods for stabilizing lipid based adjuvant formulations using glycolipids |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4107152C2 (en) * | 1991-03-06 | 1994-03-24 | Gregor Cevc | Preparations for non-invasive administration of antidiabetics |
DE4107153A1 (en) * | 1991-03-06 | 1992-09-10 | Gregor Cevc | Compsns. for application of active agents |
FR2687313A1 (en) * | 1992-02-17 | 1993-08-20 | Oreal | Dispersion of vesicles based on betaines and cosmetic or pharmaceutical compositions containing this dispersion. |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1341331A (en) * | 1972-01-17 | 1973-12-19 | Procter & Gamble | Organobismuth compound having antimicrobial properties and its use in detergent and textile-softening compositions |
GB1539625A (en) * | 1975-06-30 | 1979-01-31 | Oreal | Process for preparing aqueous dispersions of lipid spherules and aqueous dispersions of such lipid spherules |
EP0032578A1 (en) * | 1980-01-16 | 1981-07-29 | Hans Georg Prof. Dr. Weder | Process and dialysis-installation for the preparation of bilayer-vesicles and their use |
GB2089681A (en) * | 1980-12-22 | 1982-06-30 | Procter & Gamble | Process for making lipid membrane structures |
EP0067635A2 (en) * | 1981-06-15 | 1982-12-22 | THE PROCTER & GAMBLE COMPANY | Shampoo compositions |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3974076A (en) * | 1974-01-11 | 1976-08-10 | The Procter & Gamble Company | Fabric softener |
JPS6014146B2 (en) * | 1977-01-29 | 1985-04-11 | ライオン株式会社 | fiber softening composition |
JPS53134784A (en) * | 1977-04-28 | 1978-11-24 | Kao Corp | Production of small hollow cell-containing material consisting of double layers of surface active agent |
FR2416008A1 (en) * | 1978-02-02 | 1979-08-31 | Oreal | LIPOSOME LYOPHILISATES |
US4233164A (en) * | 1979-06-05 | 1980-11-11 | The Proctor & Gamble Company | Liquid fabric softener |
EP0102324A3 (en) * | 1982-07-29 | 1984-11-07 | Ciba-Geigy Ag | Lipids and surfactants in an aqueous medium |
-
1983
- 1983-09-29 JP JP58181629A patent/JPS6072831A/en active Granted
-
1984
- 1984-09-07 GB GB08422628A patent/GB2147263B/en not_active Expired
- 1984-09-27 DE DE19843435516 patent/DE3435516A1/en not_active Withdrawn
- 1984-09-28 FR FR8414910A patent/FR2552679B1/en not_active Expired - Fee Related
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1341331A (en) * | 1972-01-17 | 1973-12-19 | Procter & Gamble | Organobismuth compound having antimicrobial properties and its use in detergent and textile-softening compositions |
GB1539625A (en) * | 1975-06-30 | 1979-01-31 | Oreal | Process for preparing aqueous dispersions of lipid spherules and aqueous dispersions of such lipid spherules |
EP0032578A1 (en) * | 1980-01-16 | 1981-07-29 | Hans Georg Prof. Dr. Weder | Process and dialysis-installation for the preparation of bilayer-vesicles and their use |
GB2089681A (en) * | 1980-12-22 | 1982-06-30 | Procter & Gamble | Process for making lipid membrane structures |
EP0067635A2 (en) * | 1981-06-15 | 1982-12-22 | THE PROCTER & GAMBLE COMPANY | Shampoo compositions |
Cited By (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5023086A (en) * | 1987-03-13 | 1991-06-11 | Micro-Pak, Inc. | Encapsulated ionophore growth factors |
US4855090A (en) * | 1987-03-13 | 1989-08-08 | Micro-Pak, Inc. | Method of producing high aqueous volume multilamellar vesicles |
US4911928A (en) * | 1987-03-13 | 1990-03-27 | Micro-Pak, Inc. | Paucilamellar lipid vesicles |
US4942038A (en) * | 1987-03-13 | 1990-07-17 | Micro Vesicular Systems, Inc. | Encapsulated humectant |
US5000960A (en) * | 1987-03-13 | 1991-03-19 | Micro-Pak, Inc. | Protein coupling to lipid vesicles |
US5628936A (en) * | 1987-03-13 | 1997-05-13 | Micro-Pak, Inc. | Hybrid paucilamellar lipid vesicles |
US5234767A (en) * | 1987-03-13 | 1993-08-10 | Micro-Pak, Inc. | Hybrid paucilamellar lipid vesicles |
US4853228A (en) * | 1987-07-28 | 1989-08-01 | Micro-Pak, Inc. | Method of manufacturing unilamellar lipid vesicles |
US4917951A (en) * | 1987-07-28 | 1990-04-17 | Micro-Pak, Inc. | Lipid vesicles formed of surfactants and steroids |
WO1989000812A1 (en) * | 1987-07-28 | 1989-02-09 | Micro-Pak, Inc. | Method of manufacturing unilamellar lipid vesicles |
US5104736A (en) * | 1988-03-03 | 1992-04-14 | Micro-Pak, Inc. | Reinforced paucilamellar lipid vesicles |
US5032457A (en) * | 1988-03-03 | 1991-07-16 | Micro Vesicular Systems, Inc. | Paucilamellar lipid vesicles using charge-localized, single chain, nonphospholipid surfactants |
US5019392A (en) * | 1988-03-03 | 1991-05-28 | Micro-Pak, Inc. | Encapsulation of parasiticides |
US5160669A (en) * | 1988-03-03 | 1992-11-03 | Micro Vesicular Systems, Inc. | Method of making oil filled paucilamellar lipid vesicles |
US5019174A (en) * | 1988-03-03 | 1991-05-28 | Micro Vesicular Systems, Inc. | Removing oil from surfaces with liposomal cleaner |
WO1991004012A1 (en) * | 1989-09-21 | 1991-04-04 | Micro Vesicular Systems, Inc. | Paucilamellar lipid vesicles using charge-localized, single chain, nonphospholipid surfactants |
US5164191A (en) * | 1991-02-12 | 1992-11-17 | Micro Vesicular Systems, Inc. | Lipid vesicles having an alkyd as a wall-forming material |
US5213805A (en) * | 1991-07-25 | 1993-05-25 | Micro Vesicular Systems, Inc. | Lipid vesicles having n,n-dimethylamide derivatives as their primary lipid |
US5439967A (en) * | 1991-09-17 | 1995-08-08 | Micro Vesicular Systems, Inc. | Propylene glycol stearate vesicles |
US5405615A (en) * | 1991-09-17 | 1995-04-11 | Micro Vesicular Systems, Inc. | Sucrose distearate lipid vesicles |
US5260065A (en) * | 1991-09-17 | 1993-11-09 | Micro Vesicular Systems, Inc. | Blended lipid vesicles |
US5643600A (en) * | 1991-09-17 | 1997-07-01 | Micro-Pak, Inc. | Lipid vesicles containing avocado oil unsaponifiables |
WO1996010390A1 (en) * | 1994-09-30 | 1996-04-11 | Inex Pharmaceuticals Corp. | Novel compositions for the introduction of polyanionic materials into cells |
US5753613A (en) * | 1994-09-30 | 1998-05-19 | Inex Pharmaceuticals Corporation | Compositions for the introduction of polyanionic materials into cells |
US5785992A (en) * | 1994-09-30 | 1998-07-28 | Inex Pharmaceuticals Corp. | Compositions for the introduction of polyanionic materials into cells |
US7749520B2 (en) | 2004-07-07 | 2010-07-06 | Statens Serum Institut | Compositions and methods for stabilizing lipid based adjuvant formulations using glycolipids |
US8277823B2 (en) | 2004-07-07 | 2012-10-02 | Statens Serum Institut | Compositions and methods for stabilizing lipid based adjuvant formulations using glycolipids |
Also Published As
Publication number | Publication date |
---|---|
JPS6072831A (en) | 1985-04-24 |
GB2147263B (en) | 1987-03-25 |
DE3435516A1 (en) | 1985-04-18 |
FR2552679B1 (en) | 1993-06-11 |
FR2552679A1 (en) | 1985-04-05 |
JPH0326166B2 (en) | 1991-04-10 |
GB8422628D0 (en) | 1984-10-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
GB2147263A (en) | Compositions for making vesicles | |
Schmolka | A review of block polymer surfactants | |
Osborne et al. | Microemulsions as topical drug delivery vehicles: in‐vitro transdermal studies of a model hydrophilic drug | |
FI91217B (en) | Ophthalmological carrier composition for a pharmaceutical or diagnostic substance | |
DE60126433T2 (en) | PROCESS FOR PREPARING PHARMACEUTICAL COMPOSITIONS FOR USE WITH WEICHGELATINE FORMULATIONS | |
CA1176568A (en) | Aqueous solution containing ubidecarenon | |
GB2151203A (en) | Compositions for making vesicles | |
JPH0822815B2 (en) | Stable emulsions of highly fluorinated organic compounds | |
PT99108B (en) | METHOD FOR PREPARING A PHARMACEUTICAL COMPOSITION BASED ON PERCHUOROCARBONETS OR FLUORATED SILICONE NAOAQUOS | |
DE60014093T2 (en) | Liposome composition with protection against freeze / build damage | |
GB2359747A (en) | An anaesthetic formulation comprising micelles and propofol | |
WO1991001718A1 (en) | Method of photostabilizing eyewash and photostabilized eyewash | |
US4963363A (en) | Phospholipid delivery vehicle for aqueous-insoluble active ingredients | |
MXPA06005688A (en) | Stable liposome compositions comprising lipophilic amine containing pharmaceutical agents. | |
Ryan et al. | The preparation and characterization of liposomes containing X-ray contrast agents | |
DE3882984T2 (en) | PRODUCTION OF A SOLUTION CONSISTING OF A PHARMACOLOGICAL ACTIVE SUBSTANCE AND A LIPID. | |
JP3072340B2 (en) | Aqueous eye drops and production method thereof | |
HASHIDA et al. | Dosage form characteristics of microsphere-in-oil emulsion. II: Examination of some factors affecting lymphotropicity | |
TW201914570A (en) | Preparing method for positively-electrified charged niosome, and charged niosome | |
Guillod et al. | Vesicles made of glycophospholipids with homogeneous (two fluorocarbon or two hydrocarbon) or heterogeneous (one fluorocarbon and one hydrocarbon) hydrophobic double chains | |
JPS63297322A (en) | Production of stable ophthalmic solution containing sodium guaiazulenesulfonate | |
JPS6072829A (en) | Composition for vesicle | |
CN115957351B (en) | Iohexol injection and preparation method thereof | |
CA1214727A (en) | Injectable compositions comprising 1-(2-hydroxyethyl -5-nitro imidazole | |
JPS6075434A (en) | Composition for vesicle |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19960907 |