Agar gel bead composition and method

• US 6,319,507 B1
• Filed: 11/01/1999
• Issued: 11/20/2001
• Est. Priority Date: 05/02/1997
• Status: Expired due to Fees

• Current Assignee: Kobo Products Incorporated (Rakuten Group, Inc.)
• Original Assignee: Kobo Products Incorporated (Rakuten Group, Inc.)
• Inventors: Ding, Li, Delrieu, Pascal E.
• Primary Examiner(s): Bawa, Raj
• Application Number:
  US09/431,742
• Time in Patent Office: 750 Days
• Field of Search: 424/401, 424/484, 424/485, 424/489, 424/60, 424/70.1, 424/70.9, 424/70.28, 424/78.03, 514/937, 514/944
• US Class Current: 424/401
• CPC Class Codes: A61K 2800/56 Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms
• CPC Class Codes: A61K 8/025 Explicitly spheroidal or spherical shape
• CPC Class Codes: A61K 8/042 Gels
• CPC Class Codes: A61K 8/11 Encapsulated compositions
• CPC Class Codes: A61K 8/365 Hydroxycarboxylic acids; Ketocarboxylic acids
• CPC Class Codes: A61K 8/645 Proteins of vegetable origin; Derivatives or degradation products thereof
• CPC Class Codes: A61K 8/676 Ascorbic acid, i.e. vitamin C
• CPC Class Codes: A61K 8/73 Polysaccharides
• CPC Class Codes: A61K 8/731 Cellulose; Quaternized cellulose derivatives
• CPC Class Codes: A61K 8/735 Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
• CPC Class Codes: A61P 17/16 Emollients or protectives, e.g. against radiation
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin

Abstract

Crushable gel beads 10 formed of an agar complex provide novel cosmetic, pharmaceutical, etc. delivery vehicles for topical delivery of biologically or cosmetically active agents. Preferred agar beads 10 are complexes of a continuous phase of agar gel 12 in a self-supporting solid or semi-solid form with a restraining polymer 14. Entrapped in and dispersed randomly throughout each agar bead 10 is a water-soluble, preferably polar, restraining polymer 14, preferably a quaternized cationic polymer, such as polyquaternium 24 or steardimonium hydroxyethylcellulose. Various active agents 16 may be bound to restraining polymer 14, for example ascorbic acid, lactic acid or papain. Methods of manufacture are also described.

Claims

1. A topically applied composition comprising a two-phase cream, gel or lotion formed by homogenization at a temperature elevated above about 50°

C. of;

a) an oil phase ingredient; and

b) an aqueous phase ingredient; and

c) gel beads dispersed in the cream, gel or lotion, the gel beads comprising;

i) agar gel;

ii) a restraining polymer distributed throughout the agar gel;

iii) a topically active agent retained in the gel beads by the restraining polymer;

wherein the gel beads can be spread on application to make the active agent topically available.

2. A composition according to claim 1, the composition being formed by homogenization at a temperature elevated above about 80°

C.

3. A composition according to claim 1 wherein the active agent has at least one active agent polar group, the restraining polymer comprises polar retention groups of opposite polarity to the active agent at least one polar group whereby the active agent can bind ionically with the retention groups.

4. A composition according to claim 3 wherein the restraining polymer is a water-soluble modified polysaccharide and the retention groups are quaternary ammonium substituent groups.

5. A composition according to claim 1 wherein the active agent and the restraining polymer both comprise lipophilic groups whereby the active agent can bind lipophilically to the retention groups.

6. A composition according to claim 1 wherein the restraining polymer is dispersed randomly throughout each agar bead and is a water-soluble polymer.

7. A composition according to claim 1 wherein the restraining polymer has sufficient molecular weight to prevent egress of the restraining polymer from the agar gel has retention groups to bind the active agent to the restraining polymer for retention in the gel particles.

8. A composition according to claim 1 wherein the restraining polymer is sufficiently soluble that a desired proportion can be co-dissolved in an aqueous medium with agar in an initial bead-forming step and the restraining polymer is selected according to the character of the desired active agent, to have one or more retention groups capable of binding the active agent.

9. A composition according to claim 1 being a cosmetic formulation intended to be applied to the skin wherein the gel beads are soft enough to be crushed on the skin during normal application of the cosmetic formulation by manual spreading or massaging.

10. A composition according to claim 1 wherein the restraining polymer is selected from the group consisting of polyquaternium 24, laurdimonium hydroxyethylcellulose, cocodimonium hydroxyethylcellulose, steardimonium hydroxyethylcellulose, quaternary ammonium substituted water-soluble polysaccharides, alkyl quaternary celluloses and polypeptides having or provided with retention groups to retain the active agent and mixtures of the foregoing polymers.

11. A composition according to claim 1 wherein the active agent is selected from the group consisting of antioxidants, botanically derived polyphenols, procyanidin oligomers, free radical scavengers, topically active enzymes, antibacterials, glucose oxidase, antioxidants, superoxide dismutase, proteolytic enzymes, bromelain, DNA repair enzymes, exfoliative retinoids, retinol, retinol esters, retinol acetate, vitamin A palmitate, purified plant extracts, plant proteins, whitening agents, arbutin, essential fatty acids, linoleic acid, linolenic acid, arachidonic acid, animal proteins, collagen, elastin, keratin, moisturizers, hyaluronic acid, glycosaminoglycans, ultraviolet light filters, ultraviolet light absorbents, coated and uncoated organic and inorganic pigments, titanium, zinc, and iron oxides, melanin, sepia ink extract, colorants, dyes and perfumes.

12. A composition according to claim 11 wherein the restraining polymer is selected from the group consisting of polyquaternium 24, laurdimonium hydroxyethylcellulose, cocodimonium hydroxyethylcellulose, steardimonium hydroxyethylcellulose, quaternary ammonium substituted water-soluble polysaccharides, alkyl quaternary celluloses and polypeptides having or provided with retention groups to retain the active agent and mixtures of the foregoing polymers.

13. A composition according to claim 1 the gel beads being of from about 50 microns to 10 mm average size, being insoluble in water at 25°

C. and being formed of a polymeric gel wherein the restraining polymer is dispersed randomly in the gel, the restraining polymer has sufficient molecular weight to prevent egress of the restraining polymer from the agar gel, has retention groups to bind the active agent to the restraining polymer for retention in the gel particles and is present in a proportion sufficient to deliver an effective amount of the active agent and wherein the gel particles are manually crushable on the skin to increase the surface area of the gel particle material and expose the restraining polymer to the skin or other body surface for release of the active agent.

14. A method of preparing gel particles for incorporation in a topically applied formulation, the method comprising:

a) forming a hot aqueous solution comprising an agar gelling agent and a restraining polymer to form a gelling agent solution, the solution being gellable at a lower temperature; and

b) discharging the hot gelling agent solution through a discharge orifice into a cold hydrophobic liquid immiscible with the gelling agent solution, the cold hydrophobic liquid being maintained at a temperature below the gelling agent gelling point;

c) providing a moving stream of the cold hydrophobic liquid; and

d) discharging the hot gelling agent solution through the discharge orifice into the moving stream of cold hydrophobic liquid to generate gel particles in the hydrophobic liquid stream.

15. A method according to claim 14 comprising discharging the hot gelling agent through an injection tube, the injection tube terminating in the discharge orifice and wherein the discharge orifice is positioned in the moving stream of cold hydrophobic liquid.

16. A method according to claim 15 comprising containing the cold hydrophobic liquid in a conduit wherein the injection tube extends into the conduit.

17. A method according to claim 16 wherein the conduit has a recti-linear portion and the injection tube extends approximately perpendicularly into the recti-linear portion of the conduit.

18. A method according to claim 16 wherein the conduit has a cross-sectional area from about 4 to about 400 times the cross-sectional area of the injection tube.

19. A method according to claim 16 wherein the ratio of the flow rate of the hot gelling agent solution to the flow rate of the cold hydrophobic liquid is between about 1:

2 and 1;

50.

20. A method according to claim 16 wherein the injection tube has an internal diameter of from about 0.05 to about 10 mm.

21. A method according to claim 16 wherein the conduit has a cross-sectional area from about 4 to about 400 times the cross-sectional area of the injection tube, the ratio of the flow rate of the hot gelling agent solution to the flow rate of the cold hydrophobic liquid is between about 1:

2 and 1;

50 and the injection tube has an internal diameter of from about 0.05 to about 10 mm.

22. A method according to claim 16 wherein the hot gelling agent solution further comprises an active agent.

23. A method according to claim 14 comprising pumping the hot gelling agent solution from a heated vessel containing a bulk supply of the hot gelling agent solution to the discharge orifice.

24. A method according to claim 14 comprising recirculating the cold hydrophobic liquid through a cooled tank.

25. A method according to claim 14 comprising recirculating a coolant between a chiller and the cooled tank to maintain a desired low temperature in the tank.

26. A method according to claim 14 comprising flowing the hydrophobic liquid containing gel particles over a screen to separate the gel particles from the hydrophobic liquid.

27. A method according to claim 14 comprising pumping the hot gelling agent solution from a heated vessel containing a bulk supply of the hot gelling agent solution to the discharge orifice, recirculating the cold hydrophobic liquid through a cooled tank, recirculating a coolant between a chiller and the cooled tank to maintain a desired low temperature in the tank and flowing the hydrophobic liquid containing gel particles over a screen to separate the gel particles from the hydrophobic liquid.