Film-forming agent for drug delivery and preparation for percutaneous administration containing the same

• US 6,750,291 B2
• Filed: 04/12/2002
• Issued: 06/15/2004
• Est. Priority Date: 04/12/2002
• Status: Expired due to Fees

• Current Assignee: AmorePacific Group, Inc.
• Original Assignee: AmorePacific Group, Inc.
• Inventors: Choi, Yang Gyu, Kim, Young So, Kim, Jung Ju
• Primary Examiner(s): GORR, RACHEL F
• Application Number:
  US10/121,288
• Publication Number:
  US 20030199644A1
• Time in Patent Office: 795 Days
• Field of Search: 525/128, 524/391, 524/507, 424/449
• US Class Current: 525/128
• CPC Class Codes: C08G 18/4018 Mixtures of compounds of group C08G18/42 with compounds of group C08G18/48
• CPC Class Codes: C08G 18/4808 Mixtures of two or more polyetherdiols
• CPC Class Codes: C08L 2666/04 Macromolecular compounds according to groups C08L7/00 - C08L49/00, or C08L55/00 - C08L57/00; Derivatives thereof
• CPC Class Codes: C08L 29/10 Homopolymers or copolymers of unsaturated ethers C08L35/08 takes precedence
• CPC Class Codes: C08L 33/06 of esters containing only carbon, hydrogen and oxygen, which oxygen atoms are present only as part of the carboxyl radical
• CPC Class Codes: C08L 75/08 from polyethers

Abstract

The present invention relates to a film-forming agent which forms a film on the skin, and also to a preparation for percutaneous administration containing the film-forming agent and active ingredient. The transdermal preparation including the film-forming agent of the present invention and active ingredient exhibits excellent elasticity and flexibility, shows superior adhesion power when formed on the skin, and forms non-sticky film.

Claims

1. A film-forming agent characterized in comprising 50˜

99% by weight of the following polyurethane (A) and 1˜

50% by weight of the following addition polymerization polymer (B) having a functional group of carboxylic acid derivative;

(A) Polyurethane with weight average molecular weight of 10,000˜

500,000, which is prepared by polymerization of the following ingredient (a-1), (a-2), and (a-3), and represented with the following formula 1;

(a-1) polyethylene glycol;

(a-2) polydiol with hydroxyl groups at both ends, which has stronger hydrophobicity than the said (a-1); and

(a-3) diisocyanate having isocyanate at both ends

and

(B) The addition polymerization polymer with a functional group of carboxylic acid derivative has weight average molecular weight of 10,000˜

800,000 which contains carboxylic acid alkyl ester and/or carboxylic acid alkyl amide and/or carboxylic acid alkyl amino alkyl ester on main chain or side chain.

2. The film-forming agent as set forth in claim 1, characterized in that the said polyurethane (A) and addition polymerization polymer (B) with a functional group of carboxylic acid derivative are dissolved in a solvent applicable to skin.

3. The film-forming agent as set forth in claim 1, characterized in that the said addition polymerization polymer (B) with a functional group of carboxylic acid derivative contains on main chain or side chain carboxylic acid alkyl ester and/or carboxylic acid alkyl amide and/or carboxylic acid alkyl aminoalkyl ester, and as monomers imparting the said functional group, contains more than 10 wt % of one or more selected from the group consisting of acrylic acid alkyl ester/amide, methacrylic acid alkyl ester/amide, crotonic acid alkyl ester/amide, maleic acid alkyl ester/amide, maleic anhydride and vinyl ester.

4. The film-forming agent as set forth in claim 3, characterized in that the said acrylic acid alkyl ester monomer is selected from a group consisting of methyl acrylate, ethyl acrylate, butyl acrylate, isobutyl acrylate, isobornyl acrylate, hydroxyethyl acrylate and 2-hydroxypropyl acrylate;

acrylic acid amide monomer is selected from a group consisting of acryl amide, N-t-butylacryl amide and octyl acryl amide;

methacrylic acid alkyl ester monomer is selected from a group consisting of methyl methacrylate, ethyl methacrylate, butyl methacrylate, isobutyl methacrylate, 2-ethylhexyl methacrylate, lauryl methacrylate, hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, dimethyl aminoethyl methacrylate and t-butyl aminoethyl methacrylate;

methacrylic acid amide monomer is methacryl amidopropyl/trimethyl ammonium chloride;

maleic aicd alkyl ester is selected from a group consisting of methyl maleate, ethyl maleate, isopropyl maleate and butyl maleate;

crotonic aicd alkyl ester monomer is selected from a group consisting of methyl crotonate, ethyl crotonate, isopropyl crotonate and butyl crotonate; and

vinyl ester monomer is selected from a group consisting of vinyl acetate, vinyl propionate and vinyl neodecanoate.

5. The film-forming agent as set forth in claim 1, characterized in that the said polymer with a functional group of carboxylic acid derivative at main or side chain is selected from a group consisting of poly(methyl vinyl ether-co-maleic anhydride), poly(methyl vinyl ether-co-maleic acid ethyl ester), poly(methyl vinyl ether-co-maleic acid isopropyl ester), poly(methyl vinyl ether-co-maleic acid butyl ester), poly(dimethyl aminoethyl methacrylate-co-methacrylic acid alkyl ester), poly(methacrylic acid-co-methacrylic acid alkyl ester), poly(methacrylic acid alkyl ester-co-trimethyl aminoethyl methacrylate), poly(acrylic acid-co-ethyl acrylate-co-N-t-butyl acrylamide), poly(acrylic acid alkyl ester-co-methacrylic acid alkyl ester), poly(octyl acrylamide-co-butyl aminoethyl methacrylate-co-acrylic acid), poly(octyl acrylamide-co-butyl aminoethyl methacrylate-co-acrylic acid alkyl ester), poly(octyl acrylamide-co-butyl aminoethyl methacrylate-co-methacrylic acid), poly(octyl acrylamide-co-butyl aminoethyl methacrylate-co-methacrylic acid alkyl ester), poly(octyl acrylamide-co-acrylic acid), poly(octyl acrylamide-co-acrylic acid alkyl ester), poly(octyl acrylamide-co-methacrylic acid), poly(octyl acrylamide-co-methacrylic acid alkyl ester), poly(vinyl acetate-co-crotonic acid), and poly(vinyl acetate-co-crotonic acid-co-vinyl propionate).

6. The film-forming agent as set forth in claim 1, characterized in that weight ratio of the said polyurethane (A) and the addition polymerization polymer (B) with a functional group of carboxylic acid derivative is 50:

50˜

99;

1.

7. The film-forming agent as set forth in claim 2, characterized in that the said solvent is an aqueous alcohol solution.

8. The film-forming agent as set forth in claim 2, characterized in that the said polyurethane (A) and the addition polymerization polymer (B) with a functional group of carboxylic acid derivative are dissolved in the said solvent to be in a range of 0.1˜

50 wt %.

9. The film-forming agent as set forth in claim 1, characterized in that the said (a-2) is one or more selected from polyalkylene glycols and polyesterdiols.

10. The film-forming agent as set forth in claim 9, characterized in that the said polyalkylene glycols are selected from a group consisting of poly(propylene glycol), poly(butylene glycol), poly(tetramethylene glycol), poly(hexamethylene glycol), a triple block copolymer composed of poly(ethylene glycol) and poly(propylene glycol) (or poly(ethylene glycol)/poly(propylene glycol)/poly(ethylene glycol) or poly(propylene glycol)/poly(ethylene glycol)/poly(propylene glycol));

and the said polyesterdiols are selected from a group consisting of polycaprolactonediol, polylactonediol and polyglycolic acid diol.

11. The film-forming agent as set forth in claim 1, characterized in that the said (a-3) is one or more selected from aromatic diisocyanate and aliphatic diisocyanate.

12. The film-forming agent as set forth in claim 1, characterized in that the said film-forming agent, when forming the film upon spread to the skin, allows tensile strength of the film to be at least 0.5 Mpa, elongation % to be at least 100%, and adhesion determined by peel adhesion test of PSTC testing method to be at least 20 g/in to stainless steel.

13. A transdermal preparation, characterized by comprising the film-forming agent of claim 1;

a biocompatible solvent that can dissolve the said film-forming agent; and

active ingredient that can be delivered through skin.

14. The transdermal preparation as set forth in claim 13, characterized in that the said film-forming agent is 0.1˜

50 wt % to the said solvent, and the said active ingredient is 0.01˜

50 wt % to the total weight of the preparation.

15. The transdermal preparation as set forth in claim 13, characterized in that the said active ingredient applicable to skin is one or a mixture of two or more selected from a group consisting of non-steroidal antiphlogistic analgesic;

steroid;

local anesthetic;

antihistaminic;

antibiotic;

antifungal agent;

antiviral agent;

skeletal muscle relaxant;

keratolytic;

pimple treating agent;

skin protecting agent;

vitamins A, B, C, D, E and their pharmaceutically available derivatives;

skin whitening agent;

galenical extract;

heparin sodium; and

capsaicin.

16. The transdermal preparation as set forth in claim 15, characterized in that the said active ingredient is one or a mixture of two or more selected from a group consisting of ketoprofen, diclofenac diethylammonium, piroxicam, flubiprofen, ketorolac tromethamine, sodium fusidate, capsaicin, dipropionic acid betamethasone, clotrimazole, gentamicin sulfate, prednisolone, diphenhydramine hydrochloride, erythromycin, neomycin sulfate, heparin sodium, dexpanthenol, ketoconazole, terbinafine hydrochloride, acyclovir, tretinoin, benzoyl peroxide, kojic acid, eperisone hydrochloride, lidocaine hydrochloride, salicylic acid, lactic acid, urea, vitamin A, vitamin C, vitamin E, minoxidil and allantoin.

17. The transdermal preparation as set forth in claim 13, characterized by containing at least one additive selected from a group consisting of skin permeation enhancer, softening agent, moisturizing agent and hydrophilic polymer to increase viscosity and skin adhesion.

18. The transdermal preparation as set forth in claim 17, characterized in that the said skin permeation enhancer is one or a mixture of two or more selected from a group consisting of higher fatty acid;

higher alcohol;

polyol;

higher fatty acid ester;

fatty acid ester of glycerin;

fatty acid ether of polyethylene glycol;

fatty acid ester of polyethylene glycol;

fatty acid ether of propylene glycol;

fatty acid ester of propylene glycol;

fatty acid ester of sorbitan;

fatty acid ester of polyethylene glycol sorbitan;

terpenes;

sulfoxide;

pyrrolidone;

amide;

ethoxydiglycol, N-hydroxy methyl lactide, sorbitol, urea, squalene, squalane, olive oil, castor oil and its derivatives.

19. The transdermal preparation as set forth in claim 17, characterized in that the said moisturizing agent or softening agent is one or a mixture of two or more selected from glycerin, polyethylene glycol, propylene glycol, 1,3-butanediol, lactic acid, mineral oil, lanolin, wax and glucose derivatives.