DELIVERY OF LARGE MOLECULAR WEIGHT BIOLOGICALLY ACTIVE SUBSTANCES

• US 20140128798A1
• Filed: 05/20/2011
• Published: 05/08/2014
• Est. Priority Date: 03/29/2011
• Status: Active Grant

• Current Assignee: Photokinetix Holdings Inc.
• Original Assignee: Photokinetix Holdings Inc., Principium Europe SRL
• Inventors: Kraft, Edward R., Janson, Julien, Kulp, Gabriela, Malanchin, Rosella
• Granted Patent: US 9,474,911 B2
• Time in Patent Office: Days
• US Class Current: 604/20
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 38/30 Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2 insulin-like growth factor binding protein A61K38/1754
• CPC Class Codes: A61K 38/4893 Botulinum neurotoxin (3.4.24.69)
• CPC Class Codes: A61K 41/17 by ultraviolet [UV] or infrared [IR] light, X-rays or gamma rays
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/46 Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
• CPC Class Codes: A61K 8/0208 Tissues; Wipes; Patches
• CPC Class Codes: A61K 8/345 containing more than one hydroxy group
• CPC Class Codes: A61K 8/645 Proteins of vegetable origin; Derivatives or degradation products thereof
• CPC Class Codes: A61K 8/9717 Rhodophycota or Rhodophyta [red algae], e.g. Porphyra
• CPC Class Codes: A61K 8/9789 Magnoliopsida [dicotyledons]
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61K 9/7046 the adhesive comprising macromolecular compounds
• CPC Class Codes: A61N 2005/065 Light sources therefor
• CPC Class Codes: A61N 2005/0652 Arrays of diodes
• CPC Class Codes: A61N 2005/0659 infrared
• CPC Class Codes: A61N 2005/0661 ultraviolet
• CPC Class Codes: A61N 2005/0662 : Visible light
• CPC Class Codes: A61N 5/0613 : Apparatus adapted for a specific treatment
• CPC Class Codes: A61N 5/062 : Photodynamic therapy, i.e. excitation of an agent
• CPC Class Codes: A61Q 19/00 : Preparations for care of the skin
• CPC Class Codes: C12Y 304/24069 : Bontoxilysin (3.4.24.69), i.e. botulinum neurotoxin

Abstract

The invention relates generally to intradermal, transdermal, and/or transmembrane delivery of biologically active substances in the epidermis and/or through the skin, sub-dermal tissues, blood vessels and cellular membranes without causing damage to the cellular surface, tissue or membrane. The biologically active substances may have a molecular weight no less than about 5.8 kDa to about 2,500 kDa, such as Hyaluronic Acid (HA). The biologically active substances may be deposited in a dermal patch containing a red algae polysaccharide-based matrix, wherein the red algae polysaccharide is an extract of Chondrus crispus at 2% by weight of the dermal patch. The invention provides systems and methods for enhanced intradermal, transdermal, and/or transmembrane delivery of such biologically active substances using pulsed incoherent light. The invention further provides a device for the application of the pulsed incoherent light to cellular surfaces and membranes using those compositions and methods.

Claims

1. A device for photokinetic intradermal and/or transdermal delivery of a biologically active substance to a subject, said device comprising:

(1) a generator that provides an oscillating electrical pulse;

(2) at least one light emitting diode that receives the oscillating electrical pulse and responds by providing an incoherent light; and

,

(3) a donor cell that holds a formulation comprising the biologically active substance, wherein the donor cell is positioned to receive the incoherent light.

2-54. -54. (canceled)

55. A method for photokinetic intradermal and/or trans dermal delivery of a biologically active substance having a molecular weight of no less than 5800 Da to a subject, the method comprising:

(1) preparing a formulation comprising the biologically active substance;

(2) applying said formulation to a cellular surface on the skin of the subject;

(3) illuminating said formulation on said cellular surface with a pulsed incoherent light having a selected wavelength, pulse rate and duty cycle; and

,

(4) allowing said biologically active substance in said formulation to permeate said cellular surface, thereby effecting photokinetic intradermal and/or transdermal delivery of the biologically active substance.

62. The method of claim 55, wherein the formulation comprises a gelling agent.

64. The method of claim 55, wherein the formlulation further comprises a photocatalytic agent.

73. The method of claim 55, wherein said biologically active substance comprises sodium hyaluronate (e.g., one with a M.W. of at least about 1000 kDa, 1600 kDa, 2200 kDa, 2500 kDa, 3000 kDa, 3500 kDa, 4000 kDa, 4500 kDa, 5000 kDa).

74. The method of claim 55, wherein said biologically active substance is a cosmetic agent, or a therapeutic agent.

75. The method of claim 55, wherein said biologically active substance comprises:

(1) a peptide selected from the group consisting of Gly-Tyr, Val-TyrVal, Tyr-Gly-Gly-Phe-Met (SEQ ID NO;

     1), Tyr-Gly-Gly-Phe-Leu (SEQ ID NO;

     2), and Asp-Arg-Val-Tyr-Ile-His-Pro-Phe (SEQ ID NO;

     3);

(2) a honnone selected from the group consisting of methionine enkephalin acetate, leucine enkephalin, angiotensin II acetate, f)-estradiol, methyl testosterone, and progesterone;

or,

(3) a protein selected from the group consisting of enzymes, nonenzymes, antibodies, and glycoproteins.

77. The method of claim 55, wherein said pulsed incoherent light is selected from the group consisting of fluorescent, ultraviolet, visible, near infrared, LED (light emitting diode), and halogen light.

84. The method of claim 55, wherein said pulse rate is between about 1.7 cycles per second (cps) and about 120 cps, or about 1.7 cps and about 80 cps.

86. The method of claim 55, wherein said duty cycle is between about 50% and about 75%.

87. The method of claim 55, further comprising adjusting the transdermal flux rate of the biologically active substance by modulating the light energy.

89. The method of claim 55, wherein the formulation comprises a dermal patch, said dermal patch containing a red algae polysaccharide-based matrix, wherein said red algae polysaccharide is an extract of Chondrus crispus at 1.5%-2.5%, preferably 2% by weight of the dermal patch.

90. The method of claim 89, wherein the dermal patch further comprises methylpropanediol and glycerine as moisturising ingredients.

91. The method of claim 89, wherein the dermal patch further comprises butylene glycol and sorbitol as moisturising and/or anti-microbial ingredients.

92. The method of claim 89, wherein the dermal patch comprises water, methylpropanediol, glycerin, Chondrus crispus, and optionally a preservative.

93. The method of claim 89, wherein the dermal patch comprises (as weight %) 67% water, 10% methylpropanediol, 20% glycerin, 2% Chondrus crispus and optionally a preservative.

94. The method of claim 89, wherein the dermal patch comprises water, butylene glycol, sorbitol, Chondrus crispus and optionally a preservative.

95. The method of claim 89, wherein the dermal patch comprises (as weight %) 67% water, 10% butylene glycol, 20% sorbitol, 2% Chondrus crispus and optionally a preservative.

96. The method of claim 89, wherein the dermal patch comprises no preservative.

56-61. -61. (canceled)

63. (canceled)

65-72. -72. (canceled)

76. (canceled)

78-83. -83. (canceled)

85. (canceled)

88. (canceled)

97-101. -101. (canceled)

103. A method for photokinetic intradermal and/or transdennal delivery of a biologically active substance to a subject, the method comprising:

(1) preparing a dermal patch comprising the biologically active substance, wherein the dermal patch conlprises a red algae polysaccharide-based matrix, and wherein said red algae polysaccharide is an extract of Chondrus crispus at 2% by weight of the dermal patch;

(2) applying said dermal patch to a cellular surface on the skin of the subject;

(3) illuminating said dermal patch on said cellular surface with a pulsed incoherent light having a selected wavelength, pulse rate and duty cycle; and

,

(4) allowing said biologically active substance in said dermal patch to permeate said cellular surface, thereby effecting photokinetic intradermal and/or transdermal delivery of the biologically active substance.

104-110. -110. (canceled)