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WO1990012565A1 - Formulations aqueuses avec phospholipides - Google Patents

Formulations aqueuses avec phospholipides Download PDF

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Publication number
WO1990012565A1
WO1990012565A1 PCT/EP1990/000621 EP9000621W WO9012565A1 WO 1990012565 A1 WO1990012565 A1 WO 1990012565A1 EP 9000621 W EP9000621 W EP 9000621W WO 9012565 A1 WO9012565 A1 WO 9012565A1
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Prior art keywords
water
formulation
weight
phospholipids
acid
Prior art date
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Ceased
Application number
PCT/EP1990/000621
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English (en)
Inventor
Hans-Heiner LAUTENSCHLÄGER
Miklos Ghyczy
Joachim Röding
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A Natterman und Cie GmbH
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A Natterman und Cie GmbH
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Publication of WO1990012565A1 publication Critical patent/WO1990012565A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14—Liposomes; Vesicles
    • 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—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • A61K9/1277—Preparation processes; Proliposomes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair

Definitions

  • the invention refers to a method for the preparation of water-containing formulations with phospholipids using swelling accelerators and the application of these formulations for the preparation of liposomes.
  • Phospholipids and liposomes have been the subject of many investigations and are described in the literature in numerous publications. In these the incorporation of the phospholipids into aqueous media plays an important role on account of their economic importance. There is also great interest in the therapeutic application of liposomes as carriers of active agents of the most various types.
  • EP 98561 mixtures of phospholipids or mixtures containing phospholipids were brought into solution or emulsified by the addition of organic solvents and surfactants.
  • DE-PS 11 41 639 choline phosphoric acid diglyceride ester compounds were solubilized with the aid of salts of the bile acids.
  • DE-AS 12 27 191 lecithins were emulsified in water with aliphatic polyalcohols in the presence of ethanol.
  • DE-OS 16 17 542 deoiled crude lecithin was made water- soluble in aqueous, sugar-containing alcohol solutions.
  • oil-containing lecithins can be made dispersible in water by the addition of monoglycerides.
  • DE-PS 32 18 027 the addition of hydroxyethyl fatty acid, amides yields liquified and water-soluble phospholipids.
  • these methods have the disadvantage that they only function for specific phospholipids or particular phospholipid mixtures or lecithin mixtures and can, therefore, only be applied in a few particular cases.
  • DE-OS 36 10 873 involving the addition of specific amines can be used for the dispersion or dissolution of many phospholipids and lecithin mixtures in water, but, on account of the negative organoleptic properties (odor! and toxic properties of the dissolution agents- the amines used -, they are unsuitable for oral, parenteral or topical applications.
  • Liposomes of various compositions and sizes are obtained depending on the class of process, so that it is necessary to distinguish between numerous types.
  • the phospholipid or phospholipid mixture is dissolved in a volatile organic solvent - e.g. chloroform, ether, ethanol etc. - and the solvent is evaporated in the rotary evaporator leaving behind a thin film of phospholipid in the round-bottomed flask.
  • a volatile organic solvent e.g. chloroform, ether, ethanol etc. - and the solvent is evaporated in the rotary evaporator leaving behind a thin film of phospholipid in the round-bottomed flask.
  • the liposomes are then produced by the addition of water or a suitable buffer solution
  • Unilamellar liposomes can be produced using the "French press" at low pressures by passing multilamellar liposomes produced by conventional means through a narrow orifice (Hamilton R.L. et al., J. Lipid. Res. 21, 981-992 (1980)).
  • phospholipidsand a surface-active substance plus a solvent are used to produce solvent-lipid- detergent micelles, liposomes are produced on removal of the detergent.
  • the aim of the present invention is to create a process which allows the easy preparation of aqueous formulations of phospholipids of widely different composition and concentration for the manufacture of liposomes.
  • the aim was fulfilled according to the invention by a method of preparation of water-containing formulations with phospholipids by admixture of phospholipids in water with stirring in the presence of swelling accelerators, whereby a mixture of saturated or unsaturated organic carboxylic acids and their salts with a strong base yielding a pH of 5 to 7 is used as swelling accelerator in proportions from 1 to 30% by weight, the concentration of phospholipid is 20 to 50% by weight and the remainder water, based on the total weight of the formulation. Proportions of 1 to 10% by weight of swelling accelerator with respect to the total weight of the formulation are especially preferred.
  • Preferred saturated or unsaturated carboxylic acids are those with 10 to 20.carbon atoms of natural or synthetic origin.
  • capric acid lauric acid, myristic acid, palmitic acid, stearic acid, margaric acid, arachic acid, behenic acid, undecanoic acid, 10-undecanoic acid, tridecanoic acid, pentadecanoic acid, nonadecanoic acid, heneicosanoic acid, lauroleic acid, myristoleic acid, palmitoleic acid, petroselaidic acid, oleic acid, elaidic acid, linoleic acid, linolaidic acid, linolenic acid, eleostearic acid, gadoleic acid, arachidonic acid, erucic acid, brassidic acid, clupanodonic acid, hydroxyundecanoic acid, petrosel'inic acid, parinaric acid, 10-methyloctadecanoic acid, isotridecanoic acid (a mixture of isomeric C 13 acids), 10-
  • R 1 is hydrogen or a saturated or unsaturated acyl group with 1 to 22 carbon atoms
  • R 2 is the side chains of the amino acids of collagen and R 3 is hydrogen or an alkali metal ion and
  • n is an integer between 1 and 10.
  • Collagen mainly consists of the amino acids glycine, proline and hydroxyproline together with small amounts of glutamic acid, arginine, alanine, aspartic acid, lysine, leucine, serine and isoleucine.
  • R 2 has for the individual amino acids the following meaning:
  • R 2 - H (for glycine)
  • R 2 - CH 2 -CH 2 -CH 2 - (for proline)
  • R 2 - CH-CHOH-CH 2 - (for hydroxyproline)
  • R 2 - CH 2 -CH 2 -COOH (for glutamic acid)
  • R 2 - CH 3 (for alanine)
  • R 2 - CH 2 -COOH (for aspartic acid)
  • R 2 - ( CH 2 ) 4 - H 3 (for lysine)
  • R 2 - CH 2 -CH (CH 3 ) -CH 3 (for leucine)
  • R 2 - CH 2 OH (for serine)
  • R 2 - CH ( CH 3 ) -CH 2 -CH 3 (for isoleucine)
  • Hydrolysates or acylated hydrolysates of casein, keratin or O-acyl derivatives of hydroxyproline can also be used as the carboxylic acid.
  • Acylated amino acids, acylated peptides or choline and their salts can also serve as the carboxylic acid.
  • Suitable strong bases for the formation of the salts of the organic carboxylic acids are, in particular, sodium hydroxide, potassium hydroxide, ammonium hydroxide and amines, such as ethanolamine and triethanolamine.
  • Soya lecithin ca. 30% phosphatidylcholine, 1-2% lysophosphatidylcholine, 22% phosphatidylethanolamine, 1-2% lysophosphatidylethanolamine, 3-4% phosphatidylserine, 18% phosphatidylinositol, 13% phytoglycolipids, 2% phosphatidic acid, 8% accompanying lipids.
  • Rape lecithin 30-32% phosphatidylcholine, 3% lysophosphatidylcholine, 30-32% phosphatidylethanolamine, 2-3% lyso- phosphatidylethanolamine, 14-18% phosphatidylinositol, 1% lysophosphatidylinositol, 10% phytoglycolipids, 1% phospha- tidic acid, 2-3% accompanying lipids.
  • Safflower lecithin 32-39% phosphatidylcholine, 1-2% lyso- phosphatidylcholine, 14-17% phosphatidylethanolamine, 2% lysophosphatidylethanolamine, 21-27% phosphatidylinositol, 1% lysophosphatidylinositol, 15-28% accompanying lipids.
  • Egg lecithin 73% phosphatidylcholine, 5-6% lysophosphati- dylcholine, 15% phosphatidylethanolamine, 2-3% lysophosphatidylethanolamine, 1% phosphatidylinositol, 2-3% sphingomyeline, 1% plasmologen.
  • the individual lecithins can be purified by known methods and the phospholipids separated into their individual components such as phosphatidylcholine, phosphatidylethanol- amine, phosphatidylinositol, phosphatidylserine, phosphatidylglycerol, lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylserine, lysophosphatidylglycerol, ⁇ -acylphosphatidylethanolamine, phosphatidic acid, cardiolipin, sphingomyeline, plasmologens and other substances or into olefinic mixtures.
  • pure phospholipid products are available commercially which can have the following compositions: Phospholipon R 100 (96% phosphatidylcholine), Phospholipon R 100 H (98% phosphatidylcholine, completely hydrogenated), Phospholipon R 80 (80% phosphatidylcholine, 10% phosphatidylethanolamine), Phospholipon R 55 (55% phosphatidylcholine, 25% phosphatidylethanolamine, 2% phosphatidylinositol), Phospholipon R 38 (38% phosphatidylcholine, 16% N-acetylphosphatidylethanolamine), Phospholipon R 25 (25% phosphatidylcholine, 25% phosphatidylethanolamine, 20% phosphatidylinositol).
  • Such phospholipids can be manufactured according to the methods of EP 68 295.
  • the synthetic phospholipids that are suitable include, for example: Dihexadecanoylphosphatidylcholine, ditetradecanoylphosphatidylcholine, dioleoylphosphatidylcholine, dilinoloylphosphatidylcholine, dibutyroylphosphatidylcholine, dihexanoylphosphatidylcholine, dimyristoylphosphatidylcholine, distearoylphosphatidylcholine, but, in particular, dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylglycerol.
  • the type, amount and, if necessary, the ratio of the carboxylic acid to its salt is adjusted to the particular phospholipid or mixture of phos- pholipids.
  • the formulation should exhibit a pH of 5 to 7 in order to avoid degradation of the phospholipids or their hydrolysis to lysophospholipids.
  • the admixture of the phospholipids and any other additives and components to be incorporated can be carried out in a conventional stirring apparatus. Vigorous stirring is necessary to cause intensive mixing. Anchor stirrers, blade stirrers, propeller stirrers and turbine mixers are all employed, whereby it is advantageous to fit them with scrapers. Before the phospholipid is added it should be ensured that the apparatus is disinfected and sterilized when pyrogen-free formulations are being prepared. The mixing is carried out at room temperature or at elevated temperatures up to 50°C.
  • the aqueous phospholipid formulations prepared according to the invention can be diluted with water when they form liposomal phases or lipo- somes.
  • the formulations according to the invention are gel-like mixtures which can be diluted with water.
  • the particular advantage of the method according to the invention is that it is possible to produce the liposomes in a single piece of apparatus, namely a mixer.
  • additives such as lower alcohols (methanol, ethanol, propanol), chloroform, dichloro- methane and other volatile organic solvents can be included for the mixing process.
  • organic solvents is particularly appropriate if they are to be included in the lipid components that are to be produced later. However, it is preferable to use no solvents or only very little if they must later be removed from the formulation.
  • Other additives during admixture of the phospholipids with water can be electrolytes such as NaCl, CaCl 2 , Na 2 HPO 4 , NaHCO 3 , choline chloride, choline phosphate, sodium acetate or mixtures of these.
  • the additives are preferably included to the extent of 0 to 20% by weight of the total formulation.
  • the phospholipids can be introduced into the water in the presence of the additives but it is possible to add them in the form of an aqueous solution after the phospholipid has been introduced into the water.
  • Carbohydrates and/or starch hydrolysates, mono- and di- saccharides and mixtures of these substances can also be added to the formulations. However, these additional adjuvant substances should not make up more than 30% by weight with respect to the total formulation.
  • Antihypertensives apresoline, atenolol, captopril
  • Cancer drugs adriamycin, daunorubicin, bleomycin, azathioprine, cyclophosphamide, vin- cristine, methothrexate, vinblastin, cisplatin
  • analgesics morphium Dilaudid, codeine, codeinelike synthetics, Demerol, oxymorphone, phenobarbital, barbiturates
  • Antibiotics amoxicillin, ampicillin, carbenicillin, cefadroxil, cefazolin, cefoxitin, cephalothin, erythromycin, gentamycin, moxalactam, imipenem, penicillin, piperacillin, tetracycline, t ⁇ bramycin, vancomycin and other aminoglycosides
  • cytokines GM-CFS, M-CSF, G-CFS, inhibin, nerve growth factors, tumour growth factors, tumor tissue killing factors, Muller's inhibiting substance, insulin, collagen, fibronectin, laminin, other proteins accessible by DNA recombination
  • Immunotherapeutics interferon, interleukin-2, ⁇ -globulin, monoclonal antibodies
  • Preferred examples of pharmaceutically, cosmetically and dietetically active ingredients include, for example, the following substances for incorporation in the liposome formulation:
  • Actinomycin D acylglutamate, AD 32, adenosine triphosphate, adrenaline, adriamycin, alanine, albumin, allopurinol, aminobenzoic acid
  • Amgloglucosidase amgloglucosidase
  • angiotensin anthracyclines
  • ascorbic acid L-asparginase
  • azathioprine bacteria
  • benaxoprofen betamethasone
  • 2,3- biphosphoglycerate bitolterol mesylate
  • bromazepam acylglutamate, AD 32, adenosine triphosphate, adrenaline, adriamycin, alanine, albumin, allopurinol, aminobenzoic acid
  • amphetamine sulphate amgloglucosidase
  • angiotensin anthracyclines
  • ascorbic acid L-asparginase
  • carbazochrome carotene, casein, castor oil, chloroquine, chymotrypsin, clonazepam, coagulation factors, coenzymes, colchincine, collagen, corticosteroids, cosmetics, cyanocobalamin, cyclosporin, cytosine arabinoside, daunomycin, decaglycerol monolaurate, dexamethasone, dextran, diagnostics, diazepam, diacetyl phosphate, dihydroxyergotoxin, dihydroxyacetone, diltiazem, dipyridamole, DNA, doxorubicin, EDTA, elastin, ephedrine, epinephrine, ergot alkaloids, erythromycin, ethyl mercuriothiosalicylate, extract of aloes, ferritin, fibroin, flunitrazepam, fluocinolone acetonide, 5-flu
  • the separation of non-enclosed substances can be carried out by dialysis, gel chromatography, flotation, centrifugation or ultracentrifugation.
  • the choice of method depends on the method by which the liposomes have been prepared. Such methods are familiar to the specialist.
  • the separation of non-enclosed substances is of minor importance and is usually unnecessary when the liposomes are to be used for cosmetic purposes.
  • the separation of non-enclosed substances is of relevance when the liposome preparations are intended for pharmaceutical or medical purposes.
  • a mixture of 3 g phospholipid (containing 80% phosphatidylcholine), 0.1 g sodium stearate and 10 g demineralized water are vigorously stirred for 30 minutes at 50°C in a commercial laboratory mixer.
  • the phospholipid swells after a very short time and produces a uniform, highly viscous swollen phase with a pH of ca. 6.
  • a liposomal formulation can be produced from the gel by dilution with water.
  • a mixture of 0.1 g potassium oleate, 0.8 g oleic acid and 10 g Phospholipon 100 (highly concentrated phosphatidylcholine) in 100 g demineralized water are vigorously stirred for 30 minutes at 50°C in a laboratory mixer.
  • the phospholipid swells after a very short time and produces a uniform, viscous swollen phase with a pH of ca. 7.
  • a mixture of 10 g enriched phospholipid (containing 80% phosphatidylcholine), 0.1 g potassium oleate and 0.8 g oleic acid in 100 g demineralized water are vigorously stirred for 20 minutes at 50°C in a laboratory mixer.
  • the phospholipid swells after a very short time and produces a uniform, viscous swollen phase.
  • the pH of the swollen phase is 6.5.
  • a mixture of 0.1 g sodium stearate, 0.4 g stearic acid and 3 g Phospholipon 100 H (fully hydrogenated, highly concentrated phosphatidylcholine) in 100 g demineralized water are vigorously stirred at 80°C in a laboratory mixer.
  • the phospholipid swells after a very short time and produces a uniform, highly viscous swollen phase with a pH of ca. 8.5.
  • a mixture of 0.2 g potassium palmitate and 15 g Phospholipon 100 H (highly concentrated phosphatidylcholine) in 100 g demineralized water are vigorously stirred for 10 minutes at 50°C in a laboratory mixer.
  • a mixture of 0.2 g palmitic acid, 0.1 g triethanolamine and 15 g Phospholipon 100 H (highly concentrated phosphatidyl- choline) in 100 g demineralized water is vigorously stirred for 10 minutes at 50°C in a laboratory mixer.
  • a mixture of 0.1 g potassium oleate and 10 g phospholipid containing 80% phosphatidylcholine in 100 g demineralized water is vigorously stirred at 50°C in a laboratory mixer.
  • the phospholipid swells after a short time and forms a homogeneous, viscous swollen phase with a pH of 7.5.
  • a mixture of 0.1 g potassium oleate and 10 g phospholipid containing 50% by weight phosphatidylcholine in 100 g demin- eralized water is vigorously stirred for 30 minutes at 50°C in a laboratory mixer.
  • the phospholipid swells extensively and forms a homogeneous, viscous swollen phase with a pH of 5.7.
  • a mixture of 0.2 g potassium palmitate, 15 g Phospholipon 100 H (concentrated phosphatidylcholine) and 2 g thistle oil in 100 g demineralized water is vigorously stirred for 10 minutes at 50°C in a laboratory mixer.
  • the phospholipid swells after a short time and forms a homogeneous, viscous swollen phase with a pH of 6.5.
  • a mixture of 3.5 g Lipacide PCO (acylated collagen hydroly- sate), 0.3 g potassium hydroxide and 6 g phospholipid containing 80% by weight phosphatidylcholine in 10 g demineralized water is vigorously stirred for 10 minutes at 60°C in a laboratory mixer.
  • the phospholipid swells after a short time and forms a swollen phase with a pH of 7. It can, for example, be used as a creme base.
  • a mixture of 10.5 g Lipacide PCO (acylated collagen hydroly- sate), 0.4 g sodium hydroxide, 3 g phospholipid containing 80% by weight phosphatidylcholine and 283 g demineralized water is vigorously stirred for 10 minutes at 60°C in a laboratory mixer.
  • the swollen phase formed in a short time has a pH of 6 and can, for example, be used as a lotion for cosmetic purposes.
  • the water-containing formulations according to the invention described in examples 2 to 12 can be converted into liposomal formulations by dilution with water.
  • the direct preparation of liposomal formulations via the swollen phase will be described in the examples that follow:
  • a mixture of 0.5 g citric acid, 0.3 g sodium hydroxide, 10 g anhydrous glucose and 100 g demineralized water is vigorously stirred in a suitable mixer and 30 g Phospholipon 100 (highly concentrated phophatidylcholine) is worked homogene- ously into the solution at room temperature.
  • the pH is 6.5.
  • a liposomal formulation is produced with a mean particle size of 100 nm.
  • a mixture of 143 g 10% sodium hydroxide solution, 100 g Lipacide PCO (acylated collagen hydrolysate), 375 g phospholipid with 80% by weight phosphatidylcholine and 4018 g demineralized water is homogenized intensively in a mixer for 30 minutes and then mixing is continued while 300 g 15% sodium chloride solution is worked in.
  • a liposomal formulation is produced with a pH of 6.4 and a particle size of ca. 129 nm.
  • the liposomal formulation is very suitable for cosmetic purposes, for example as a base for skin care or similar preparations.
  • the storage life can be increased by the addition of a preservative, for instance 1 g Kathon CG.
  • a mixture of 4.4 g 10% sodium hydroxide solution, 6 g phospholipid, 22.5 g Phosal 80 and 264 g demineralized water are homogenized intensively in a mixer for 30 minutes and then mixing is continued while 2.7 g sodium chloride is worked in.
  • a liposomal formulation is produced which is suitable for cosmetic purposes, e.g. skin care preparations and hair rinses.
  • the pH of the formulation is 6.1 and, hence, it is very gentle to the skin.
  • the mean particle size is 120 nm.
  • the formulation can also contain 0.06 g Kathon CG as preservative to prolong its storage life.
  • a mixture of 1.3 g 10% sodium hydroxide solution, 1.5 g phospholipid, 22 g Phosal 80 and 272 g demineralized water is homogenized intensively in a suitable mixer for 60 minutes and then mixing is continued while 2.7 sodium chloride is worked in.
  • the liposomal formulation which is produced has a pH of 6.3 and a mean particle size of 150 nm. It is suitable for cosmetic purposes.
  • the formulation can also contain 0.06 g Kathon CG as preservative.
  • Example 17 A mixture of 2 g 10% sodium hydroxide solution, 6 g phospholipid, 22.5 g Phosal 80 and 267 g demineralized water is homogenized intensively in a mixer for 60 minutes and 2.7 g sodium chloride is added. After the sodium chloride has been worked in a liposomal formulation is produced which has a pH of 5.6 and a mean particle size of 134 nm. The formulation is very gentle to the skin and can be used for cosmetic purposes. The formulation can also contain 0.06 g Kathon CG as preservative.

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Abstract

Procédé pour préparer des formulations aqueuses de phospholipides en présence d'accélérateurs de gonflement et utilisation des gels obtenus par ce procédé pour préparer des formulations de liposomes en diluant les gels dans de l'eau.
PCT/EP1990/000621 1989-04-25 1990-04-18 Formulations aqueuses avec phospholipides Ceased WO1990012565A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE3913513 1989-04-25
DEP3913513.6 1989-04-25

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Publication Number Publication Date
WO1990012565A1 true WO1990012565A1 (fr) 1990-11-01

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PCT/EP1990/000621 Ceased WO1990012565A1 (fr) 1989-04-25 1990-04-18 Formulations aqueuses avec phospholipides

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CN (1) CN1046848A (fr)
IL (1) IL94103A0 (fr)
WO (1) WO1990012565A1 (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4005711C1 (fr) * 1990-02-23 1991-06-13 A. Nattermann & Cie Gmbh, 5000 Koeln, De
EP0488142A1 (fr) * 1990-11-29 1992-06-03 B. Braun Melsungen AG Procédé pour encapsuler des principes actifs lipophiles solides ou liquides dans des liposomes phospholipidiques ainsi que des médicaments contenant ces liposomes
EP0509338A1 (fr) * 1991-04-12 1992-10-21 Merz & Co. GmbH & Co. Fabrication et utilisation de préparations stables de liposomes de petite taille
EP0535567A1 (fr) * 1991-10-01 1993-04-07 B. Braun Melsungen AG Liposomes contenant des anéstésiques d'inhalation volatiles, leurs préparations et leurs utilisations
WO1995003787A1 (fr) * 1993-07-28 1995-02-09 University Of Saskatchewan Vesicules lipidiques multilamellaires biphasiques
US5853755A (en) * 1993-07-28 1998-12-29 Pharmaderm Laboratories Ltd. Biphasic multilamellar lipid vesicles
FR2780887A1 (fr) * 1998-07-08 2000-01-14 Jean Noel Thorel Solution aqueuse saline et mineralisee, et son utilisation en cosmetique et dermo-pharmacie
FR2782638A1 (fr) * 1998-08-28 2000-03-03 Shiseido International France Utilisation en cosmetique d'acides gras
WO2001013887A3 (fr) * 1999-08-25 2001-09-20 Merckle Gmbh Gel phospholipidique
WO2006096998A1 (fr) * 2005-03-15 2006-09-21 Remo Stoop Agent servant a supprimer des tatouages
CN103720653A (zh) * 2012-10-12 2014-04-16 天津药物研究院 一种长春瑞滨亚微乳注射液及其制备方法
WO2017142834A1 (fr) * 2016-02-15 2017-08-24 Kemin Industries, Inc. Matériaux lipophiles hydrosolubles
US12036286B2 (en) 2021-03-18 2024-07-16 Seagen Inc. Selective drug release from internalized conjugates of biologically active compounds

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Publication number Priority date Publication date Assignee Title
CN103798845A (zh) * 2014-03-05 2014-05-21 青岛金海源食品有限公司 一种利用鳕鱼骨开发纳米胶原蛋白钙的方法

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EP0088046A2 (fr) * 1982-02-17 1983-09-07 Ciba-Geigy Ag Lipides en phase aqueuse
FR2540381A1 (fr) * 1983-02-08 1984-08-10 Dior Sa Parfums Christian Procede pour stimuler la croissance des cellules; composition cosmetique, pharmaceutique et composition complementaire pour milieu de culture cellulaire appliquant ce procede
FR2597345A1 (fr) * 1986-04-22 1987-10-23 Oreal Composition cosmetique ou pharmaceutique a base d'une dispersion aqueuse de spherules lipidiques.
FR2609393A1 (fr) * 1988-02-23 1988-07-15 Serobiologiques Lab Sa Composition notamment utile comme matiere de base pour la preparation de compositions pharmaceutiques, notamment dermatologiques et/ou cosmetiques comprenant une substance azotee, notamment aminoacides, oligo- ou polypeptides, proteines, et leurs derives, et composition pharmaceutique ou cosmetique ainsi preparee.

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0088046A2 (fr) * 1982-02-17 1983-09-07 Ciba-Geigy Ag Lipides en phase aqueuse
FR2540381A1 (fr) * 1983-02-08 1984-08-10 Dior Sa Parfums Christian Procede pour stimuler la croissance des cellules; composition cosmetique, pharmaceutique et composition complementaire pour milieu de culture cellulaire appliquant ce procede
FR2597345A1 (fr) * 1986-04-22 1987-10-23 Oreal Composition cosmetique ou pharmaceutique a base d'une dispersion aqueuse de spherules lipidiques.
FR2609393A1 (fr) * 1988-02-23 1988-07-15 Serobiologiques Lab Sa Composition notamment utile comme matiere de base pour la preparation de compositions pharmaceutiques, notamment dermatologiques et/ou cosmetiques comprenant une substance azotee, notamment aminoacides, oligo- ou polypeptides, proteines, et leurs derives, et composition pharmaceutique ou cosmetique ainsi preparee.

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991012794A1 (fr) * 1990-02-23 1991-09-05 Nattermann, A. & Cie. Gmbh Dispersion de vesicules phospholipides aqueuse, procede de preparation et utilisation
DE4005711C1 (fr) * 1990-02-23 1991-06-13 A. Nattermann & Cie Gmbh, 5000 Koeln, De
EP0488142A1 (fr) * 1990-11-29 1992-06-03 B. Braun Melsungen AG Procédé pour encapsuler des principes actifs lipophiles solides ou liquides dans des liposomes phospholipidiques ainsi que des médicaments contenant ces liposomes
EP0509338A1 (fr) * 1991-04-12 1992-10-21 Merz & Co. GmbH & Co. Fabrication et utilisation de préparations stables de liposomes de petite taille
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WO2000002530A1 (fr) * 1998-07-08 2000-01-20 Thorel Jean Noel Solution aqueuse saline et mineralisee, et son utilisation en cosmetique et dermo-pharmacie
FR2782638A1 (fr) * 1998-08-28 2000-03-03 Shiseido International France Utilisation en cosmetique d'acides gras
EP0985409A1 (fr) * 1998-08-28 2000-03-15 Shiseido International France SA Utilisation en cosmétique d'acides gras
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WO2006096998A1 (fr) * 2005-03-15 2006-09-21 Remo Stoop Agent servant a supprimer des tatouages
CN103720653A (zh) * 2012-10-12 2014-04-16 天津药物研究院 一种长春瑞滨亚微乳注射液及其制备方法
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CN1046848A (zh) 1990-11-14
IL94103A0 (en) 1991-01-31

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