EP1207854A1 - Preserved liposomes - Google Patents

Preserved liposomes

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Publication number
EP1207854A1
EP1207854A1 EP00959298A EP00959298A EP1207854A1 EP 1207854 A1 EP1207854 A1 EP 1207854A1 EP 00959298 A EP00959298 A EP 00959298A EP 00959298 A EP00959298 A EP 00959298A EP 1207854 A1 EP1207854 A1 EP 1207854A1
Authority
EP
European Patent Office
Prior art keywords
composition
amount
preserved
cosmetic composition
weight
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.)
Withdrawn
Application number
EP00959298A
Other languages
German (de)
French (fr)
Inventor
Durant B. Scholz
Geoffrey J. Brooks
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Arch Personal Care Products LP
Original Assignee
Arch Personal Care Products LP
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Arch Personal Care Products LP filed Critical Arch Personal Care Products LP
Publication of EP1207854A1 publication Critical patent/EP1207854A1/en
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
    • 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
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A61K8/676—Ascorbic acid, i.e. vitamin C
    • 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
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin

Definitions

  • the present invention relates to the preservation of liposomal preparations against microbial contamination. More particularly, the present invention relates to a cosmetic liposomal preparations containing active ingredients which have previously been difficult to preserve, such as magnesium ascorbyl phosphate.
  • Liposomes are spherical vesicles composed of lipid bilayers. Active ingredients inside the liposomes can be delivered to the skin by topical application of the liposomes.
  • a general reference for the application of liposomes to cosmetics is Hayward, J.A. and Smith, W.P. Potential Applications of Liposomes in Cosmetic Science, in Cosmetic and Toiletries, 105:47-54, 1990.
  • U.S. Pat. No. 5,585,109 to Hayward et al. teaches the cosmetic delivery of un-neutralized salicylic acid by a liposome formulation including a preservative.
  • Liposome formulations are typically difficult to preserve against microbiological contamination.
  • An 8-week challenge study is considered a standard measure of preservative efficacy within the cosmetic industry. All percentages given in the specification are percent by weight of the total composition weight, unless otherwise noted.
  • a preserved cosmetic composition comprising: a) a vesicle-forming amount of lipids known to form, either alone or in combination, unilamellar vesicles; b) a cosmetic-effective amount of an active ingredient; c) a preservative-effective amount of a combination of sorbic acid and salicylic acid or water-soluble salts thereof; d) a base in an amount which provides a pH of about 5 to about 6 to the composition; and e) water.
  • the cosmetic liposomes of the invention can optionally contain other ingredients conventionally employed in cosmetic products.
  • ingredients include, but are not limited to, perfumes, colorants such as staining dyes and pigments, humectants, anti- dandruff agents, anti-acne agents, germicides, sunscreens, emollients, vitamins, sterols and other lipids.
  • Preferred lipids include the synthetic or natural phospholipids, phosphatidylthanolamines, phosphatidylserines, cereamides, cerebrosides, phophatidylglycerides and non-ionic surfactants.
  • Particularly preferred lipids are natural phospholipids such as soya lecithin, in an amount of 0.5 to 10%.
  • Most preferred are natural phospholipids which have been substantially purified to increase the phosphatidylcholine content.
  • Preferred active ingredients include any ingredient known for cosmetic use through topical application.
  • active ingredients for use in the cosmetic liposomes of the invention include, but are not limited to, vitamins, herbal extracts, enzymes, growth factors, anti-dandruff agents, anti-acne agents, germicides and sterols.
  • a "cosmetic-effective amount" of an active ingredient is that amount which is required in a liposome preparation for the active ingredient to have a discernible cosmetic effect upon topical application.
  • a "preservative-effective amount" of a combination of sorbic acid and salicylic acid or water-soluble salts thereof is at least 0.1% of sorbic acid or a water-soluble salt of sorbic acid in combination with at least 0.1% of salicylic acid or a water-soluble salt of salicylic acid.
  • sorbic acid is present in an amount from 0.1% to 5%
  • salicylic acid or its water-soluble salt are present in an amount from 0.1% to 10%.
  • the base used may be either organic or inorganic.
  • a liposome composition of the cosmetic active ingredient magnesium ascorbyl phosphate is preserved by the addition of sorbic acid and salicylic acid.
  • Previously known preservative systems were unsuccessful in preserving liposome compositions of magnesium ascorbyl phosphate.
  • Magnesium ascorbyl phosphate functions to deliver a stabilized form of Vitamin C (ascorbic acid) to the skin.
  • the stabilized Vitamin C functions as an antioxidant, skin tightener and pigment promoter.
  • EXAMPLE 1 Mg Ascorbyl Phosphate Liposomes Preserved with 0.2% Salicylic Acid and 0.2% Sorbic Acid
  • the sorbic acid and the salicylic acid were dissolved in water.
  • the pH was then adjusted to a pH of 5.5 using the base.
  • the active ingredient, Mg ascorbyl phosphate, was then added.
  • the lecithin is added under agitation, and the mixture is processed by high shear homogenization or microfulidization until a particle size of between 100 nm and 300 nm is reached.
  • the particle size was monitored by a Horiba LA-90 particle size analyzer (Horiba Instruments, Inc., Irvine, California).
  • Mg ascorbyl phosphate liposomes were also prepared using two prior art preservatives, Phenonip (Nipa-Hardwicke, Inc., Wilmington, Deleware), and the combination of Dowicil (Dow Chemical USA, Midland, Michigan), methyl paraben and propyl paraben.
  • Phenonip Napa-Hardwicke, Inc., Wilmington, Deleware
  • Dowicil Dowicil
  • the Phenonip was dissolved in water.
  • the lecithin is added under agitation, and the mixture is processed by high shear homogenization or microfiilidization until a particle size of between 100 nm and 300 nm is reached.
  • the particle size was monitored by a Horiba LA-90 particle size analyzer.
  • the Dowicil 200, methyl paraben and propyl paraben were dissolved in water.
  • the active ingredient, Mg ascorbyl phosphate, was then added.
  • the lecithin is added under agitation, and the mixture is processed by high shear homogenization or microfiilidization until a particle size of between 100 nm and 300 nm is reached.
  • the particle size was monitored by a Horiba LA-90 particle size analyzer.
  • Comparative Example 2 were each inoculated with standardized cultures to provide a final concentration of 5.0 x 10 5 gram positive bacteria per gram, 5.0 x 10 5 gram negative bacteria per gram, 5.0 x 10 5 yeast per gram and 5.0 x 10 4 mold spores per gram.
  • the inoculum was distributed uniformly throughout the preserved samples in a manner which minimized aeration. The samples were then stored at room temperature for the duration of the eight week study.
  • each sample was taken one week after the first inoculation and every week thereafter until the eighth week.
  • Each portion was diluted and plated on a series of petri dishes containing media which were selective for each of gram positive bacteria, gram negative bacteria, yeast and mold.
  • the series of plates were then incubated. Following incubation, the number of colonies on the plates was determined using a colony counter and used to calculate the number of organisms per gram for each class of gram positive bacteria, gram negative bacteria, yeast and mold.
  • the salicylic acid/sorbic acid of Example 1 provided a stable preservative for the liposomes, even in the face of repeated challenges with bacteria, yeast, and mold spores.
  • the phenonip preserved and Dowicil 200/methyl paraben/propyl paraben preserved liposomes failed to provide adequate protection from even one challenge.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • Dermatology (AREA)
  • Cosmetics (AREA)

Abstract

The invention is directed to a preserved cosmetic composition comprising lipid vesicles having lumens, in which the lipid vesicle lumens include a cosmetic-effective amount of an active ingredient; a preservative-effective amount of a combination of sorbic acid and salicylic acid or water-soluble salts thereof; a base in an amount which provides a lipid vesicle lumen pH of about 5 to about 6; and water.

Description

PRESERVED LIPOSOMES BACKGROUND OF THE INVENTION
The present invention relates to the preservation of liposomal preparations against microbial contamination. More particularly, the present invention relates to a cosmetic liposomal preparations containing active ingredients which have previously been difficult to preserve, such as magnesium ascorbyl phosphate.
Liposomes are spherical vesicles composed of lipid bilayers. Active ingredients inside the liposomes can be delivered to the skin by topical application of the liposomes. A general reference for the application of liposomes to cosmetics is Hayward, J.A. and Smith, W.P. Potential Applications of Liposomes in Cosmetic Science, in Cosmetic and Toiletries, 105:47-54, 1990. U.S. Pat. No. 5,585,109 to Hayward et al. teaches the cosmetic delivery of un-neutralized salicylic acid by a liposome formulation including a preservative.
Liposome formulations are typically difficult to preserve against microbiological contamination. An 8-week challenge study is considered a standard measure of preservative efficacy within the cosmetic industry. All percentages given in the specification are percent by weight of the total composition weight, unless otherwise noted. SUMMARY OF THE INVENTION
It is therefore an object of the present invention to provide a preserved liposomal composition, particularly a topical formulation, that ensures against microbial growth during storage, even in the presence of added microbial contaminants. Other objects and features of the present invention will become apparent when considered in combination with the following summary and detailed description of certain preferred embodiments of the present invention.
The foregoing and related objects are achieved by providing a preserved cosmetic composition comprising: a) a vesicle-forming amount of lipids known to form, either alone or in combination, unilamellar vesicles; b) a cosmetic-effective amount of an active ingredient; c) a preservative-effective amount of a combination of sorbic acid and salicylic acid or water-soluble salts thereof; d) a base in an amount which provides a pH of about 5 to about 6 to the composition; and e) water. The cosmetic liposomes of the invention can optionally contain other ingredients conventionally employed in cosmetic products. Examples of other ingredients include, but are not limited to, perfumes, colorants such as staining dyes and pigments, humectants, anti- dandruff agents, anti-acne agents, germicides, sunscreens, emollients, vitamins, sterols and other lipids. Once the liposome composition has been formed such that the interior of the liposomes, the limposome lumens, contain the active ingredient and the combination of sorbic acid and salicylic acid in a pH of about 5 to about 6, one of skill in the art is well able to alter the characteristics of the solution exterior to the liposomes by the addition of compounds, dilution, dialysis or other known methods, without altering the content of the liposomes. Preferred lipids include the synthetic or natural phospholipids, phosphatidylthanolamines, phosphatidylserines, cereamides, cerebrosides, phophatidylglycerides and non-ionic surfactants. Particularly preferred lipids are natural phospholipids such as soya lecithin, in an amount of 0.5 to 10%. Most preferred are natural phospholipids which have been substantially purified to increase the phosphatidylcholine content. Preferred active ingredients include any ingredient known for cosmetic use through topical application. Examples of active ingredients for use in the cosmetic liposomes of the invention include, but are not limited to, vitamins, herbal extracts, enzymes, growth factors, anti-dandruff agents, anti-acne agents, germicides and sterols. A "cosmetic-effective amount" of an active ingredient is that amount which is required in a liposome preparation for the active ingredient to have a discernible cosmetic effect upon topical application.
A "preservative-effective amount" of a combination of sorbic acid and salicylic acid or water-soluble salts thereof is at least 0.1% of sorbic acid or a water-soluble salt of sorbic acid in combination with at least 0.1% of salicylic acid or a water-soluble salt of salicylic acid. Preferably, sorbic acid is present in an amount from 0.1% to 5%, and salicylic acid or its water-soluble salt are present in an amount from 0.1% to 10%.
The base used may be either organic or inorganic. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
In a preferred embodiment, a liposome composition of the cosmetic active ingredient magnesium ascorbyl phosphate is preserved by the addition of sorbic acid and salicylic acid. Previously known preservative systems were unsuccessful in preserving liposome compositions of magnesium ascorbyl phosphate.
Magnesium ascorbyl phosphate functions to deliver a stabilized form of Vitamin C (ascorbic acid) to the skin. The stabilized Vitamin C functions as an antioxidant, skin tightener and pigment promoter. EXAMPLE 1 Mg Ascorbyl Phosphate Liposomes Preserved with 0.2% Salicylic Acid and 0.2% Sorbic Acid
Ingredient Content Substantially Purified Soya Lecithin 80 grams
Sorbic Acid 2 grams
Salicylic Acid 2 grams
NaOH to pH 5.5
Water QS to 1 kilogram Mg Ascorbyl Phosphate 10 grams
To compound the formula, the sorbic acid and the salicylic acid were dissolved in water. The pH was then adjusted to a pH of 5.5 using the base. The active ingredient, Mg ascorbyl phosphate, was then added. Finally, the lecithin is added under agitation, and the mixture is processed by high shear homogenization or microfulidization until a particle size of between 100 nm and 300 nm is reached. The particle size was monitored by a Horiba LA-90 particle size analyzer (Horiba Instruments, Inc., Irvine, California).
As a comparison for testing, Mg ascorbyl phosphate liposomes were also prepared using two prior art preservatives, Phenonip (Nipa-Hardwicke, Inc., Wilmington, Deleware), and the combination of Dowicil (Dow Chemical USA, Midland, Michigan), methyl paraben and propyl paraben. COMPARATIVE EXAMPLE 1 Mg Ascorbyl Phosphate Liposomes Preserved with 1.0% Phenonip
Ingredient Content
Substantially Purified Soya Lecithin 80 grams Phenonip 10 grams
Water QS to 1 kilogram
Mg Ascorbyl Phosphate 10 grams
To compound the formula, the Phenonip was dissolved in water. The active ingredient, Mg ascorbyl phosphate, was then added. Finally, the lecithin is added under agitation, and the mixture is processed by high shear homogenization or microfiilidization until a particle size of between 100 nm and 300 nm is reached. The particle size was monitored by a Horiba LA-90 particle size analyzer.
COMPARATIVE EXAMPLE 2 Mg Ascorbyl Phosphate Liposomes Preserved with 0.2% Dowicil 200, 0.2% Methyl Paraben, 0.05% Propyl Paraben
Ingredient Content
Substantially Purified Soya Lecithin 80 grams Dowicil 200 2 grams
Methyl Paraben 2 grams Propyl Paraben 0.5 grams
Water QS to 1 kilogram
Mg Ascorbyl Phosphate 10 grams
To compound the formula, the Dowicil 200, methyl paraben and propyl paraben were dissolved in water. The active ingredient, Mg ascorbyl phosphate, was then added. Finally, the lecithin is added under agitation, and the mixture is processed by high shear homogenization or microfiilidization until a particle size of between 100 nm and 300 nm is reached. The particle size was monitored by a Horiba LA-90 particle size analyzer.
EXAMPLE 2 Eight Week Challenge Study of Preservative Effectiveness Samples of the preserved liposome compositions of Example 1, Comparative Example
1 and Comparative Example 2 were each inoculated with standardized cultures to provide a final concentration of 5.0 x 105 gram positive bacteria per gram, 5.0 x 105 gram negative bacteria per gram, 5.0 x 105 yeast per gram and 5.0 x 104 mold spores per gram. The inoculum was distributed uniformly throughout the preserved samples in a manner which minimized aeration. The samples were then stored at room temperature for the duration of the eight week study.
A portion of each sample was taken one week after the first inoculation and every week thereafter until the eighth week. Each portion was diluted and plated on a series of petri dishes containing media which were selective for each of gram positive bacteria, gram negative bacteria, yeast and mold. The series of plates were then incubated. Following incubation, the number of colonies on the plates was determined using a colony counter and used to calculate the number of organisms per gram for each class of gram positive bacteria, gram negative bacteria, yeast and mold.
The fourth week after the inoculation, after the weekly portion was removed for diluting and plating, the samples were reinoculated with standardized cultures to provide an additional 5.0 x 105 gram positive bacteria per gram, 5.0 x 105 gram negative bacteria per gram, 5.0 x 105 yeast per gram and 5.0 x 104 mold spores per gram.
If, at any point during the challenge study, the number of colonies on the series of plates from a sample were too numerous to count (TNTC), this indicated a failure of the preservative system, and the study was discontinued for that sample. The results of the eight week challenge study are shown in Table 1, below.
Table 1
20 As can be seen from Table 1, the salicylic acid/sorbic acid of Example 1 provided a stable preservative for the liposomes, even in the face of repeated challenges with bacteria, yeast, and mold spores. In contrast, the phenonip preserved and Dowicil 200/methyl paraben/propyl paraben preserved liposomes failed to provide adequate protection from even one challenge.
25 The invention has been described in connection with certain preferred embodiments which illustrate the principals of the invention. However, it should be understood that various modifications and changes may readily occur to those skilled in the art, and it is not intended to so limit the invention. Accordingly, modifications and equivalents may be considered as falling within the scope of the invention as defined by the claims hereinbelow.

Claims

WHAT IS CLAIMED IS:
1. A preserved cosmetic composition comprising lipid vesicles having lumens, wherein the lipid vesicle lumens contain: a) a cosmetic-effective amount of an active ingredient; b) a preservative-effective amount of a combination of sorbic acid and salicylic acid or water-soluble salts thereof; c) a base in an amount which provides a lipid vesicle lumen pH of about 5 to about 6; and d) water.
2. The preserved cosmetic composition of claim 1, wherein the active ingredient is magnesium ascorbyl phosphate.
3. The preserved cosmetic composition of claim 1, wherein the sorbic acid is present in an amount of at least 0.1% by weight of the composition and the salicylic acid or water soluble salt thereof is present in an amount of at least 0.1% by weight of the composition.
4. The preserved cosmetic composition of claim 1, wherein the sorbic acid is present in the amount of from about 0.1% to about 5.0 % by weight of the composition and the salicylic acid or water soluble salt thereof is present in the amount of from about 0.1% to about 10% by weight of the composition.
5. The preserved cosmetic composition of claim 1, wherein the lipid vesicles have a particle size of from about 100 to about 300 nm.
6. A preserved cosmetic composition comprising: a) an vesicle-forming amount of lipids known to form, either alone or in combination, unilamellar vesicles; b) a cosmetic-effective amount of an active ingredient; c) a preservative-effective amount of a combination of sorbic acid and salicylic acid or water-soluble salts thereof; d) a base in an amount which provides a pH of about 5 to about 6 to the composition; g and e) water.
7. The preserved cosmetic composition of claim 6, wherein the active ingredient is magnesium ascorbyl phosphate.
5 8. The preserved cosmetic composition of claim 6, wherein the sorbic acid is present in an amount of at least 0.1% by weight of the composition and the salicylic acid or water soluble salt thereof is present in an amount of at least 0.1% by weight of the composition.
9. The preserved cosmetic composition of claim 6, wherein the sorbic acid is present in 10 the amount of from about 0.1% to about 5.0 % by weight of the composition and the salicylic acid or water soluble salt thereof is present in the amount of from about 0.1% to about 10% by weight of the composition.
10. The preserved cosmetic composition of claim 6, wherein the lipid vesicles have a particle size of from about 100 to about 300 nm.
15 11. The preserved cosmetic composition of claim 6, wherein the lipids are natural phospholipids in an amount of about 0.5 to about 10% by weight of the composition.
12. The preserved cosmetic composition of claim 11, wherein the natural phospholipids are soya lecithin.
EP00959298A 1999-09-03 2000-08-22 Preserved liposomes Withdrawn EP1207854A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US390411 1982-06-22
US39041199A 1999-09-03 1999-09-03
PCT/US2000/022985 WO2001017507A1 (en) 1999-09-03 2000-08-22 Preserved liposomes

Publications (1)

Publication Number Publication Date
EP1207854A1 true EP1207854A1 (en) 2002-05-29

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP00959298A Withdrawn EP1207854A1 (en) 1999-09-03 2000-08-22 Preserved liposomes

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EP (1) EP1207854A1 (en)
JP (1) JP2003535030A (en)
WO (1) WO2001017507A1 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006124300A (en) * 2004-10-27 2006-05-18 Takasago Internatl Corp Vesicle preparation
US9375388B2 (en) 2011-09-23 2016-06-28 Indian Institute Of Technology, Bombay Nanoparticle based cosmetic composition

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4643939A (en) * 1986-03-04 1987-02-17 Shiseido Company Ltd. Oil absorbing cosmetic tissue
US5498420A (en) * 1991-04-12 1996-03-12 Merz & Co. Gmbh & Co. Stable small particle liposome preparations, their production and use in topical cosmetic, and pharmaceutical compositions
FR2687314A1 (en) * 1992-02-18 1993-08-20 Oreal LIPID VESICLE DISPERSION, COSMETIC AND / OR PHARMACEUTICAL COMPOSITION CONTAINING THE SAME, AND PROCESS FOR THE PREPARATION OF SAID DISPERSION.
EP0616799B1 (en) * 1993-03-24 2000-05-03 COLLABORATIVE LABORATORIES Inc. Cosmetic delivery system for salicylic acid and process for preparation of same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0117507A1 *

Also Published As

Publication number Publication date
WO2001017507A1 (en) 2001-03-15
JP2003535030A (en) 2003-11-25

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