WO2008010241A1 - A liposomal complex of sodium carboxymethyl beta-glucan - Google Patents

A liposomal complex of sodium carboxymethyl beta-glucan Download PDF

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Publication number
WO2008010241A1
WO2008010241A1 PCT/IT2006/000543 IT2006000543W WO2008010241A1 WO 2008010241 A1 WO2008010241 A1 WO 2008010241A1 IT 2006000543 W IT2006000543 W IT 2006000543W WO 2008010241 A1 WO2008010241 A1 WO 2008010241A1
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Prior art keywords
sodium carboxymethyl
beta glucan
carboxymethyl beta
liposomal complex
complex
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PCT/IT2006/000543
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French (fr)
Inventor
Luigi Mercuri
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D.M.G. Italia Srl
Mibelle Ag Biochemistry
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Priority to EP06780590A priority Critical patent/EP2051698A1/en
Priority to PCT/IT2006/000543 priority patent/WO2008010241A1/en
Publication of WO2008010241A1 publication Critical patent/WO2008010241A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • 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

Definitions

  • the .present invention relates to preparation and use of a liposomal CM-glucan (carboxymethiled glucan) complex in dermatological, oral or ophtalmic application. More particular, the invention describes the method of including CM-glucan in small transparent phospholipidic vesicles.
  • the CM-glucan molecules are encapsulated in the core of the liposomes or stick to the liposome membrane forming a specific complex which improves the penetration of CM-glucan into the skin and increases the bioavailability into cells.
  • This phosphoglucan complex also improves the bioavailability of CM-Glucan upon oral or ophthalmic applications and gives a synergistic effect together with lecithin. Crude extracts from yeast have been used for a long time for cosmetic and pharmaceutical purposes. These products have been found useful in treating various diseases and skin conditions [1] .
  • Glucan is a ⁇ - (1-3) -linked polyglucose of high molecular weight and belongs to the class of drugs known today as biological response modifiers. Glucan from baker's yeast is a very potent stimulator of the immune system by activating macrophages and other cells. Therefore, glucan preparations have been extensively studied in wound healing [3] , infectivology
  • Glucan isolated from the cell wall of baker's yeast is a water insoluble particulate polymer which is not suitable for topical applications. Therefore a carboxymethyled glucan (CM- Glucan) has been developed to obtain a water soluble product.
  • CM- Glucan carboxymethyled glucan
  • the carboxymethylation takes place under specific conditions in a reaction that yields a product with a substitution degree of 0.75 +/- 0.15 [8]. Evaluation of the activity of CM-Glucan
  • Glucan preparations have been shown to be active at very low concentrations. WoIk et al. found a significant acceleration in wound healing by topical application of a glucan preparation at 0.01% [3].
  • CM-Glucan sodium carboxymethyl beta glucan
  • CM-Glucan solutions can counteract these signs of aging by significantly improving skin elasticity and skin roughness [11] .
  • CM-Glucan Despite all these positive effects of CM-Glucan on the skin the application of CM-Glucan in topical, oral or ophthalmologic use has been limited due to a poor bioavailability of the large molecular weight polysaccharide.
  • the ionic water-soluble sodium salt of carboxymethylated glucan has difficulties to enter cells and bind to membranes.
  • nanoparticles agents [12].
  • the technique of high pressure homogenization permits the industrial production of high quality vesicle dispersions for cosmetic and other uses.
  • Particle size, surface charge and payload determine the properties of the preparation and their application.
  • Liposomes and nanoparticles have become an indispensable component of today's advanced personal care products and have acquired a permanent place in cosmetic formulations.
  • the phospholipids forming these carriers enhance the penetration of the active agents into the stratum corneum and therefore increase their bioavailability.
  • lecithin is also an excellent skin softening and moisturizing agent itself.
  • sensitive compounds can be protected with these structures.
  • 60 g soy lecithin with a content of 80% phosphatidylcholine are dispersed in 1 1 of a solution of 25% glycerin in water containing 0.5% Hydroxymethylglycineate as a preservative.
  • the lecithin dispersion is homogenized at 1200 bar 2 times using a Microfluidizer to prepare liposomes.
  • the particle size of the liposomes are analyzed with a photon correlation spectrometer.
  • the average particle size zav was 50 nm.
  • CM-Glucan solution 1 1 of the CM-Glucan solution is mixed with 1 1 of the liposomes.
  • the mixture is homogenized again at 1200 bar
  • the final preparation forms a liposomal CM-Glucan complex with a particle size of 50 +/- 30 nm.
  • the particle size of the liposomes are analyzed with a photon correlation spectrometer.
  • the average particle size zav was 30 nm.
  • CM-Glucan solution 1 1 of the CM-Glucan solution is mixed with 1 1 of the liposomes.
  • the mixture is homogenized again at 1200 bar 4 times using a Microfluidizer .
  • the final preparation forms a liposomal CM-Glucan complex with a particle size of 40 +/- 20 nm.
  • the lecithin dispersion is homogenized at 1200 bar 4 times using a Microfluidizer to prepare liposomes .
  • the particle size(s) of the liposomes is (are) analyzed with a photon correlation spectrometer.
  • the average particle size zav was 40 nm.
  • 1 1 of the CM-Glucan solution is mixed with 1 1 of the liposomes.
  • the mixture is homogenized again at 1200 bar 2 times using a Microfluidizer .
  • the final preparation forms a liposomal CM-Glucan complex with a particle size of 60 +/- 30 nm.
  • the preparation is transparent and can be heat sterilized for 20 minutes at 121° Celsius to be used for example in ophthalmic applications .
  • the preparation called "Phosphoglucan” is transparent and can be filtered through 1-5 ⁇ m membranes to be used for example in ophthalmic applications Properties of Phosphoglucan
  • the Phosphoglucan formulations prepared according to the protocols of Example . 1-3 or similar are transparent products with low viscosities and can easily be formulated into water-based consumer products as described below. The products are stable for 12 - 36 months and do not change appearance.
  • CM-Glucan molecules are encapsulated in the core of the liposomes or stick to the liposome membrane forming a specific complex which improves the penetration of CM-Glcuan into the skin and increases "the bioavailability into cells.
  • This phosphoglucan complex also improves the bioavailability of CM-Glucan upon oral or ophthalmic applications and gives a synergistic effect together with lecithin.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Molecular Biology (AREA)
  • Dermatology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Medicinal Preparation (AREA)
  • Cosmetics (AREA)

Abstract

A method of including CM-glucan in small transparent phospholipidic vesicles. The CM-glucan molecules are encapsulated in the core of the liposomes or stick to the liposome membrane forming a specific complex which improves the penetration of CM-glucan into the skin and increases the bioavailability into cells. This phosphoglucan complex also improves the bioavailability of CM-Glucan upon oral or ophthalmic applications and gives a synergistic effect together with lecithin.

Description

A LIPOSOMAL COMPLEX OF SODIUM CARBOXYMETHYL
BETA-GLUCAN
The .present invention relates to preparation and use of a liposomal CM-glucan (carboxymethiled glucan) complex in dermatological, oral or ophtalmic application. More particular, the invention describes the method of including CM-glucan in small transparent phospholipidic vesicles. The CM-glucan molecules are encapsulated in the core of the liposomes or stick to the liposome membrane forming a specific complex which improves the penetration of CM-glucan into the skin and increases the bioavailability into cells. This phosphoglucan complex also improves the bioavailability of CM-Glucan upon oral or ophthalmic applications and gives a synergistic effect together with lecithin. Crude extracts from yeast have been used for a long time for cosmetic and pharmaceutical purposes. These products have been found useful in treating various diseases and skin conditions [1] .
In 1941, investigations of yeast components led to the discovery of the first defined pharmaceutical yeast product, Zymosan [2] . Further studies have shown that water insoluble Zymosan has immune-stimulating activity. This product is a raw cell wall preparation composed of glucan, other polysaccharides, proteins and lipids. Over the last two decades, glucan from yeast cell walls has been identified as a single immunologically active component.
Glucan is a β- (1-3) -linked polyglucose of high molecular weight and belongs to the class of drugs known today as biological response modifiers. Glucan from baker's yeast is a very potent stimulator of the immune system by activating macrophages and other cells. Therefore, glucan preparations have been extensively studied in wound healing [3] , infectivology
[4] and oncology [5, 6]. In all these applications, different β- (1-3) -glucan preparations from yeast have been shown to be very active.
Recently, the good tolerability and efficacy of a soluble yeast glucan has been proven in a phase II study [7] . The application of the soluble glucan preparation before and after thoracic or abdominal surgery lowered postoperative infection rates.
Glucan isolated from the cell wall of baker's yeast (Saccharomyces cerevisiae) is a water insoluble particulate polymer which is not suitable for topical applications. Therefore a carboxymethyled glucan (CM- Glucan) has been developed to obtain a water soluble product. The carboxymethylation takes place under specific conditions in a reaction that yields a product with a substitution degree of 0.75 +/- 0.15 [8]. Evaluation of the activity of CM-Glucan
Glucan preparations have been shown to be active at very low concentrations. WoIk et al. found a significant acceleration in wound healing by topical application of a glucan preparation at 0.01% [3].
The protective effect of sodium carboxymethyl beta glucan (CM-Glucan) regarding oxidative stress in human skin cells could be demonstrated by measuring intracellular glutathione and ferritin concentrations as endpoints [9] . These cell culture experiments showed that CM-Glucan is able to protect keratinocytes from the depletion of antioxidant molecules.
The pretreatment of the skin with formulations containing CM-Glucan resulted in a significant reduction of the peroxidation of squalene. The addition of only 0.04% CM-Glucan to the oil-in-water emulsions resulted in a 59% inhibition of the squalene peroxidation. An almost complete protection (94.9%) against UV-A induced oxidation could be observed with a product containing 0.2% CM-Glucan [10].
In general, with advancing age, the number and activity of immuno-competent cells (Langerhans cells and keratinocytes) in the epidermis is decreased which makes the skin more susceptible to environmental hazards. In the dermis, a loss of elastin fibrils and soluble collagen can be observed. As a result, the skin appears wrinkled and has lost its , elasticity. The topical application of CM-Glucan solutions can counteract these signs of aging by significantly improving skin elasticity and skin roughness [11] .
Despite all these positive effects of CM-Glucan on the skin the application of CM-Glucan in topical, oral or ophthalmologic use has been limited due to a poor bioavailability of the large molecular weight polysaccharide. The ionic water-soluble sodium salt of carboxymethylated glucan has difficulties to enter cells and bind to membranes.
The aim of this patent therefore was to develop a new product to overcome these limitation of CM-Glucan. Preparation of a liposomal CM-Glucan complex "Phosphoglucan" Phospholipids from soy hav.e successfully been used to prepare small vesicular carriers for topical application of hydrophilic (liposomes) and lipophilic
(nanoparticles) agents [12]. The technique of high pressure homogenization permits the industrial production of high quality vesicle dispersions for cosmetic and other uses.
Particle size, surface charge and payload determine the properties of the preparation and their application.
Liposomes and nanoparticles have become an indispensable component of today's advanced personal care products and have acquired a permanent place in cosmetic formulations. The phospholipids forming these carriers enhance the penetration of the active agents into the stratum corneum and therefore increase their bioavailability. At the same time, lecithin is also an excellent skin softening and moisturizing agent itself. Furthermore, sensitive compounds can be protected with these structures.
However, these carriers have not yet been applied widely in other products such as oral drugs and food supplements or ophthalmic preparations. Specially, the encapsulation of charged and/or high molecular weight molecules remained unsolved. These molecules tend to destroy the vesicular structures and cause large particles and turbid preparations. The use of liposomal vesicles in oral or ophthalmic preparations however requires transparent preparations achieved by filtration. Preparations with large vesicles or disrupted structures cannot be filtered accordingly. The following invention describes the preparation and application of small liposomal vesicles complexes with CM-Glucan which offer new opportunities in dermatological, oral or ophthalmic applications. Example 1
20 g of Sodium Carboxymethyl Beta-Glucan are dissolved in 11 purified water and stirred for 1 h at Room Temperature
60 g soy lecithin with a content of 80% phosphatidylcholine are dispersed in 1 1 of a solution of 25% glycerin in water containing 0.5% Hydroxymethylglycineate as a preservative.
After 4 h the lecithin dispersion is homogenized at 1200 bar 2 times using a Microfluidizer to prepare liposomes.
The particle size of the liposomes are analyzed with a photon correlation spectrometer.
The average particle size zav was 50 nm.
1 1 of the CM-Glucan solution is mixed with 1 1 of the liposomes. The mixture is homogenized again at 1200 bar
2 times using a Microfluidizer. The final preparation forms a liposomal CM-Glucan complex with a particle size of 50 +/- 30 nm.
The preparation called "Phosphoglucan" is transparent and can be filtered through 1-5 μm membranes to be used for ' example in ophthalmic applications . Example 2
40 g of Sodium Carboxymethyl Beta-Glucan are dissolved in 11 purified water and stirred for 1 h at
Room Temperature. The product is preserved with 1% Sodium Benzoate and the pH was adjusted at 5.0.
100 g soy lecithin with a content of 50% phosphatidylcholine are dispersed in 1 1 of a solution of 10% alcohol in water. After 4 h the lecithin dispersion is homogenized at 1200 bar 8 times using a Microfluidizer to prepare liposomes .
The particle size of the liposomes are analyzed with a photon correlation spectrometer. The average particle size zav was 30 nm.
1 1 of the CM-Glucan solution is mixed with 1 1 of the liposomes. The mixture is homogenized again at 1200 bar 4 times using a Microfluidizer . The final preparation forms a liposomal CM-Glucan complex with a particle size of 40 +/- 20 nm.
The preparation called "Phosphoglucan" is transparent and can be filtered through 1-5 μm membranes to be used for example in ophthalmic applications . Example 3
20 g of Sodium Carboxymethyl Beta-Glucan are dissolved in 11 purified water and stirred for 1 h at RT
40 g soy lecithin with a content of 80% phosphatidylcholine are dispersed in 1 1 of a solution of 15% glycerin and 10% alcohol in water.
After 4 h the lecithin dispersion is homogenized at 1200 bar 4 times using a Microfluidizer to prepare liposomes . The particle size(s) of the liposomes is (are) analyzed with a photon correlation spectrometer. The average particle size zav was 40 nm. 1 1 of the CM-Glucan solution is mixed with 1 1 of the liposomes. The mixture is homogenized again at 1200 bar 2 times using a Microfluidizer . The final preparation forms a liposomal CM-Glucan complex with a particle size of 60 +/- 30 nm.
The preparation is transparent and can be heat sterilized for 20 minutes at 121° Celsius to be used for example in ophthalmic applications . The preparation called "Phosphoglucan" is transparent and can be filtered through 1-5 μm membranes to be used for example in ophthalmic applications Properties of Phosphoglucan The Phosphoglucan formulations prepared according to the protocols of Example . 1-3 or similar are transparent products with low viscosities and can easily be formulated into water-based consumer products as described below. The products are stable for 12 - 36 months and do not change appearance. The CM-Glucan molecules are encapsulated in the core of the liposomes or stick to the liposome membrane forming a specific complex which improves the penetration of CM-Glcuan into the skin and increases "the bioavailability into cells. This phosphoglucan complex also improves the bioavailability of CM-Glucan upon oral or ophthalmic applications and gives a synergistic effect together with lecithin. References 1. Hansel, R. Polysaccharide die immun-stimulierend wirken: Eine Uebersicht ϋber entsprechende Fertigarzneimittel. Farmaceutisch Tijdschrift voor Belgie 64, 313-326 (1987)
2. Pillemer, L. and Ecker, E. E. Anticomplementary factor in fresh yeast. J. Biol. Chem. 137, 139-142 (1941)
3. WoIk, M. and Danon, D. Promotion of wound healing by yeast glucan evaluated on single animals. Med. Biol. 63, 73-80 (1985)
4. Kokashis, P. L., Williams, D. L., Cook, J. A. and Di Luzio, N. R. Increased resistance to staphylococcus aureus infection and enhancement in serum lysozyme activity by glucan. Science 199, 1340-1342 (1978)
5. Di Luzio, N. R., Williams, D. L., McNamee, R. B., Edwards, B. F. and Kitahama, A. Comparative tumor- inhibitory and anti-bacterial activity of soluble and particulate glucan. Int. J. Cancer 24, 773-779 (1979)
6. Hofer, M., Pospisil, M., Bohacek, J., Pipalova, I. and Sandula, J. Enhancement by carboxymethylglucan of early cellular damage in 1 Gy-irradiated mice. Folia Biologica Praha 41, 112-117 (1995)
7. Babineau, T. J., Hackford, A., Kenler, A., Bistrian, B., Forse, R.A., Fairchild, P. G., Heard, S., Keroack, M., Caushaj , P. and Benotti, P. A phase II multicenter, double-blind, randomized, placebo- controlled study of three dosages of an immunomodulator (PGG-Glucan) in high-risk surgical patients. Arch. Surg. 129, 1204-1210 (1994)
8. Zϋlli, F. and Suter, F. EP 0819 703Bl
9. Zϋlli, F., Applegate, L. A., Frenk, E. and Suter, F. Photoprotective effects of CM-Glucan on cultured human skin cells. Eurocosmetics 11, 46-50 (1995) 10. Zulu, F., Suter, F., Biltz, H., Nissen, H. P. and Birman, M. Carboxymethylated β- (1-3) -Glucan. Cosmetics and Toiletries 111, 91-98 (1996)
11. Zϋlli, F. and Suter, F US 6,342,486 Bl
12 Zϋlli, F. and Suter, F. Preparation of small lipid nanoparticles for topical applications. Proceed. Intern. Symp. Control. ReI. Bioact . Mater., 21, 459- 460, 1994

Claims

Claims
1. An ophthalmic preparation containing a liposomal complex of sodium carboxymethyl beta glucan.
2. An oral preparation containing a liposomal complex of sodium carboxymethyl beta glucan.
3. A cosmetic preparation containing a liposomal complex of sodium carboxymethyl beta glucan.
4. An ophthalmic preparation, according to claim 1 wherein the effective amount of the liposomal complex of sodium carboxymethyl beta glucan is a concentration in the range of 0.01% to 50% by weight .
5. An oral preparation, according to claim 2, wherein the effective amount of the liposomal complex of sodium carboxymethyl beta glucan is a concentration in the range of 0.01% to 50% by weight.
6. A cosmetic preparation, according to claim 3 wherein the effective amount of the liposomal complex of sodium carboxymethyl beta glucan is a concentration in the range of 0.01% to 50% by weight.
7. An ophthalmic preparation, according to claim 1, wherein the effective amount of the liposomal complex of sodium carboxymethyl beta glucan is a concentration in the range of 0.1% to 5% by weight .
8. An oral preparation, according to claim 2, wherein the effective amount of the liposomal complex of sodium carboxymethyl beta glucan is a concentration in the range of 0.1% to 5% by weight .
9. A cosmetic preparation, according to claim 3, wherein the effective amount of the liposomal complex of sodium carboxymethyl beta glucan is a concentration in the range of 0.1% to 5% by weight .
10. An ophthalmic preparation containing a liposomal complex of sodium carboxymethyl beta glucan according to any of claims 1,4,7, wherein this preparation has eye moisturizing properties.
11. An ophthalmic preparation containing a liposomal complex of sodium carboxymethyl beta glucan according to any of claims 1,4,7, wherein this preparation protects the eye against irritations.
12. An oral preparation containing a liposomal complex of sodium carboxymethyl beta glucan according to any of claims 2,5,8, wherein this preparation stimulates the non-specific immune system of the body.
13. A cosmetic preparation containing a liposomal complex of sodium carboxymethyl beta glucan according to any of claims 3,6,9, wherein this preparation stimulates the skin's own self protecting capacity.
14. A cosmetic preparation containing a liposomal complex of sodium carboxymethyl beta glucan according to any of claims 3,6,9, wherein this preparation rejuvenates the skin.
15. An ophthalmic preparation containing a liposomal complex of sodium carboxymethyl beta glucan according to claims 1,4,7 wherein this complex is prepared by homogenizing a solution of sodium carboxymethyl beta glucan together with a preparation of small liposomes in water or water/glycerine/alcohol mixtures forming transparent and stable liposomes of small particle size which can be filtered through 1-5 μm membranes .
16. An oral preparation containing a liposomal complex of sodium carboxymethyl beta glucan according to claims 2,5,8 wherein this complex is prepared by homogenizing a solution of sodium carboxymethyl beta glucan together with a preparation of small liposomes in water or water/glycerine/alcohol mixtures forming transparent and stable liposomes of small particle size which can be filtered through 1-5 μm membranes.
17. A cosmetic preparation containing a liposomal complex of sodium carboxymethyl beta glucan according to claims 3,6,9 wherein this complex is prepared by homogenizing a solution of sodium carboxymethyl beta glucan together with a preparation of small liposomes in water or water/glycerine/alcohol mixtures forming transparent and stable liposomes of small particle size which can be filtered through 1-5 μm membranes .
18. An ophthalmic preparation containing a liposomal complex of sodium carboxymethyl beta glucan according to claim 15 wherein the liposomes have a particle size of less than 100 nm.
19. An oral preparation containing a liposomal complex of sodium carboxyitiethyl beta glucan according to claim 16 wherein the liposomes have a particle size of less than 100 nru.
20. A cosmetic preparation containing a liposomal complex of sodium carboxymethyl beta glucan according to claim 17 wherein the liposomes have a particle size of less than 100 ran.
21. An ophthalmic preparation containing a liposomal complex of sodium carboxymethyl beta glucan according to claim 15, wherein the liposomes have a particle size of less than 50 ran.
22. An oral preparation containing a liposomal complex of sodium carboxymethyl beta glucan according to claim 16, wherein the liposomes have a particle size of less than 50 nm.
23. A cosmetic preparation containing a liposomal complex of sodium carboxymethyl beta glucan according to claim 17, wherein the liposomes have a particle size of less than 50 nm.
24. An ophthalmic preparation containing a liposomal complex of sodium carboxymethyl beta glucan according to any of claims 15,18,21, wherein the liposomal complex of sodium carboxymethyl beta glucan contains between 0.1 % and 5% sodium carboxymethyl beta glucan and between 0.1% and 10% lecithin.
25. An oral preparation containing a liposomal complex of sodium carboxymethyl beta glucan according to any of claims 16,19,22, wherein the liposomal complex of sodium carboxymethyl beta glucan contains between 0.1 % and 5% sodium carboxymethyl beta glucan and between 0.1% and 10% lecithin.
26. A cosmetic preparation containing a liposomal complex of sodium carboxymethyl beta glucan according to any of claims 17,20,23, wherein the
5 liposomal complex of sodium carboxymethyl beta glucan contains between 0.1% and 5% sodium carboxymethyl beta glucan and between 0.1% and 10% lecithin.
27. A liposomal complex of sodium carboxymethyl betaC) glucan characterized by the fact that this complex is prepared by homogenizing a solution of sodium carboxymethyl beta glucan together with a preparation of small liposomes in water or water/glycerine/alcohol mixtures forming5 transparent and stable liposomes of small particle size which can be filtered through 1-5 μm membranes .
28. A liposomal complex of sodium carboxymethyl beta glucan according to claim 27, characterized by the fact that the liposomal complex of sodium carboxymethyl beta glucan contains between 0.1 % and 5% sodium carboxymethyl beta glucan and between 0.1% and 10% lecithin.
29. A liposomal complex of sodium carboxymethyl beta glucan according to claims 27 and 28, characterized by the fact that the liposomes have a particle size of less than 100 nm.
30. A liposomal complex of sodium carboxymethyl beta glucan according to claim 27 and 28, characterized by the fact that the liposomes have a particle size of less than 50 nm.
PCT/IT2006/000543 2006-07-18 2006-07-18 A liposomal complex of sodium carboxymethyl beta-glucan WO2008010241A1 (en)

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US20110318406A1 (en) * 2010-06-23 2011-12-29 Eley Crispin G S Lecithin carrier vesicles and methods of making the same
ITFI20100159A1 (en) * 2010-07-27 2012-01-28 Pasquali S R L COMPOSITION FOR THE TREATMENT AND PREVENTION OF THE HERPES SIMPLEX LABIALE.
ITRM20120275A1 (en) * 2012-06-13 2013-12-14 Noos S R L ASSOCIATION OF RESVERATROLO AND CARBOSSIMETILGLUCANO.
US10874702B2 (en) * 2014-03-13 2020-12-29 Procare Health Iberia, S.L. Topical compositions comprising extract of Coriolus versicolor for autoimmunity enhancement
US11419800B2 (en) 2019-12-06 2022-08-23 JLABS Beauty LLC Topical compositions containing rose oil and cannabidiol and methods of making and using the same
US11890260B2 (en) 2020-05-22 2024-02-06 Ilera Derm LLC Compositions for treating acne and dermatological conditions

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