JP-2022510007-A5 -

Dates

Publication Date

20221205

Application Date

20191126

Description

(Equal portions) Those skilled in the art will recognize many equivalents of the specific embodiments of the invention described herein, or can confirm them by mere experimental means. The scope of the invention is not intended to be limited to the above description, but is set forth in the following claims. The present invention also includes the following aspects and embodiments. [1] A method comprising the step of applying an emulsion composition containing a large drug having a molecular weight of 100,000 Da or more to a site in combination with microneedle skin conditioning (MSC) of the site using a microneedle array having a microneedle density in the range of about 2 to about 50 microneedles/cm². [2] The method according to [1], wherein the density of microneedles is in the range of approximately 2 to approximately 10 microneedles/ cm² . [3] The method according to [1], wherein the density of microneedles is in the range of approximately 2 to approximately 35 microneedles/ cm² . [4] The method according to [1], wherein the composition containing a large drug comprises a nanoemulsion containing the large drug. [5] The method according to [1], wherein the composition containing a large drug comprises a macroemulsion containing a large drug. [6] The method according to any one of [1] to [5], further comprising the administration of a non-irritating osmotic agent. [7] The method according to [6], wherein a non-irritating penetration enhancer is selected from carrier peptides and copolymers. [8] The method according to any one of [6] to [7], wherein the non-irritating penetration enhancer is selected from a cationic peptide having the sequence RKKRRQRRRG-(K) 15 -GRKKRRQRRR and a positively charged carrier. [9] The method according to any one of [1] to [8], wherein site MSCs are performed before application of a composition containing a large drug to the site. [10] The method according to any one of [1] to [8], wherein site MSCs are performed after application of a composition containing a large drug to the site. [11] The method according to any one of [1] to [8], wherein the application of the site MSC and the composition containing the large drug to the site occurs substantially simultaneously. [12] The method according to any of [1] to [11], wherein the major drug is botulinum toxin. [13] The method according to [12], further comprising delivering botulinum toxin together with a biologically active substance. [14] The method according to [13], wherein the biologically active substance is selected from steroids, retinoids, anesthetics, fillers, silicones and/or collagen. [15] The method according to [14], wherein the biologically active substance is selected from hydrocortisone, retin-A and/or lidocaine. [16] The method according to any of [1] to [11], wherein the main drug is an antibody drug. [17] The method according to [16], wherein the antibody drug is selected from anti-TNFα antibody, anti-CD2 antibody, anti-CD4 antibody, anti-IL-12 antibody, anti-IL-17 antibody, anti-IL-22 antibody and anti-IL-23 antibody. [18] The method according to any one of [16] to [17], wherein the antibody drug is selected from antibodies having an epitope-binding element found in one or more of the following: infliximab, adalimumab, golimumab, etanercept, etanercept-szzs, certolizumab pegol, ciprizumab, zanolimumab, briakinumab, secukinumab, brodalumab, fezakinumab, ustekinumab and/or guselkumab. [19] The method according to any one of [16] to [17], further comprising delivering an antibody drug together with a biologically active substance. [20] The method according to any one of [16] to [19], further comprising delivering an antibody drug together with a non-irritating penetration enhancer. [21] The method according to [20], wherein a non-irritating penetration enhancer is selected from copolymers and carrier peptides. [22] A method according to any one of [1] to [21], wherein the site MSC is achieved using a device comprising multiple needles. [23] The method according to [22], wherein the device is a patch, roller, stamp or pen. [24] The method according to any one of [1] to [23], wherein the site is a skin surface covering the muscle or muscle group of the body. [25] The method according to any one of [1] to [24], wherein the site is the skin surface including sweat glands. [26] The method according to any one of [1] to [25], wherein the site is the skin surface including the sebaceous glands. [27] The method according to any one of [1] to [26], wherein the site is the skin surface including the hair follicle. [28] The method according to any one of [22] to [27], wherein the needle is of sufficient length to protrude through the stratum corneum of the skin. [29] The method according to any of [22]–[28], wherein the needle is of insufficient length to reach the nerves in the dermis of the skin. [30] The method according to any of [22] to [29], wherein the needle length is approximately 10 μm to approximately 4000 μm. [