LONG TERM DRUG DELIVERY BY TATTOO

Abstract

Provided are methods for long term drug delivery by tattoo. The bioactive agent, which comprises the drug, is delivered to a layer, or multiple layers, of the skin. Such a method allows for long-term drug activity the bioactive agent has a longer residence time within the skin when compared to routine delivery methods. Moreover, the bioactive agent may also be combined and mixed with a coloring composition, which signals the amount of bioactive agent that has been administered and if a reapplication of the bioactive agent is necessary. Also described are methods of utilizing such a drug delivery mechanism in order to effect cosmetic changes, such as enhancing hair growth by utilizing bioactive agents suited for enabling hair growth.

Claims

1. A method for delivering a bioactive agent, the method comprising: providing an oscillating needle that is fluidly connected to a composition comprising a bioactive agent; and administering the bioactive agent with the oscillating needle into a layer of skin, wherein the layer of skin is dermal, epidermal, or subcutaneous tissue; and the bioactive agent has a residence time of at least 24 hours in the layer of skin.

2. The method of claim 1, wherein the bioactive agent comprises one or more of: hair growth agents; antiviral agents; anti-infectives; antibiotics; antiviral agents; antifungal agents; antibacterial agents; antipruritics; anticancer agents, antipsychotics; cholesterol- or lipid-reducing agents; cell cycle inhibitors; anticancer agents; anti-parkinsonism drugs; HMG-CoA inhibitors; antirestenosis agents; anti-inflammatory agents; antiasthmatic agents; anthelmintic; immunosuppressives; muscle relaxants; antidiuretic agents; vasodilators; nitric oxide; nitric oxide-releasing compounds; beta-blockers; hormones; antidepressants; decongestants; calcium channel blockers; bone growth factors; bone morphogenic proteins; wound healing agents; analgesics; local anesthetic agents; antihistamines; sedatives; angiogenesis-promoting agents; angiogenesis-inhibiting agents; tranquilizers; sunscreen compositions; radiation blocking material; ultraviolet protection agents; chemotherapeutical agents, or combinations thereof.

3. The method of claim 2, wherein the bioactive agent is triamcinolone, triamcinolone acetonide, methylprednisolone, betamethasone, betamethasone acetate, sodium phosphate, dexamethasone sodium phosphate, hydrocortisone sodium succinate, dexamethasone sodium phosphate, cortisone, hydrocortisone, cortisone acetate, prednisone, cortodoxone, desoxycortone, imiquimod, minoxidil, alfatradiol, dutasteride, finasteride, bicalutamide, cyproterone acetate, flutamide, spironolactone, topilutamide, amifampridine, nepidermin, tofacitinib, ruxolitinib, baricitinib, PD4 inhibitors, calcineurin inhibitors, prostaglandin analogues, or any derivatives or combinations thereof.

4. The method of claim 1, wherein the dosage of the bioactive agent delivered ranges from about 1.010.sup.20 mL to about 2 mL per injection.

5. The method of claim 1, wherein the pH of the bioactive agent composition delivered ranges from about two to about ten.

6. The method of claim 1, wherein the bioactive agent is mixed with a coloring composition.

7. The method of claim 6, wherein the coloring composition is selected from the group consisting of heavy metal ink mixtures, metal oxide mixtures, azo-chemical mixtures, naptha-derived chemical mixtures, carbon, and mixtures comprising other natural pigments.

8. The method of claim 1, wherein the bioactive agent has a residence time of at least 48 hours in the layer of skin.

9. The method of claim 1, wherein the bioactive agent is applied to skin at depths of from about 0.1 mm to about 10 mm.

10. The method of claim 1, wherein the oscillating needle is a tattoo needle.

11. The method of claim 10, wherein the tattoo needle is selected from the group consisting of round shaders, round liners, super tight round liners, extra super tight round liners, flats, magnums, curved magnums, or stacked magnums.

12. The method of claim 10, wherein the tattoo needle comprises a diameter of from about 0.15 mm to about 0.50 mm.

13. The method of claim 10, wherein the tattoo needle comprises at least one tattoo needle point.

14. The method of claim 13, wherein the number of tattoo needle points ranges from one to 100, or from 3 to 15 needle points.

15. The method of claim 10, wherein the needle comprises a taper point length of from about 1.5 mm to about 8 mm.

Description

EXAMPLES

Example 1

Treatment of Alopecia

[0040] A suspension of minoxidil suspension at 5 wt % is created in a PEG 400 vehicle. As a control minoxidil is added to water to saturation. The test and control agents are delivered by tattoo machine to the dermis on independent sides of the face (either beard, eyebrow, or scalp) of the same subject once every 2 months for 6 months (i.e. 3 administrations). Three different subjects were tested. The side that was treated in the beard or scalp had approximately 300% more terminal (thick, strong) hairs per unit area, after 6 months (3 sessions). This compares to a comparable required administration of minoxidil solution per prior uses (every 2 weeks or every 4 weeks).

Example 2

Treatment of Vitiligo

[0041] To evaluate the ability of the process to treat vitiligo in a subject suffering the condition, one or more Janus kinase inhibitors may be administered by the tattooing process. A suspension of tofacitinib may be made in PEG such as PEG 400 or other suitable polymer. Alternatively, PEG may be covalently bound to tofacitinib via a desired linker. The resulting bioactive agent composition may then be administered at a 2 weight percent (wt %) concentration of the tofacitinib to a desired area of the skin of the subject direct to the dermal layer by a tattoo machine. It is expected that pigmentation in 90% of patches will be resolved in the first 6 months. As a placebo control, this may be compared to a second region of skin with NaCl0.9 wt % followed by tofacitinib cream 2 wt % twice a day for the same period. As is expected by control only 25% regimentation is observed.

Example 3

Treatment of Psoriasis

[0042] A composition of methotrexate at 25 mg/ml is prepared in polyethylene glycol. This is administered to subjects at the site of psoriatic plaques by tattoo machine directly to the dermal layer. Administration will be once every 3 months for 9 months. As a control, subjects will be administered 25 mg/ml methotrexate by injection once a month for the same period. Subjects undergoing the tattoo administration of the increased residence time methotrexate will show clearance following the first treatment session. Control subjects will suffer traditional side effects such as increased liver enzymes and show similar levels of clearance as the tattoo administration.

Example 4

Treatment of Basal Cell Carcinoma (BCC)

[0043] A composition of vismodegib is prepared in suspension with polyethylene glycol. This is administered to subjects at the site of carcinoma by tattoo machine. Administration will be once a week for 6 months. As a control, subjects will be administered vismodegib orally for the same period. Subjects undergoing the tattoo administration of the increased residence time vismodegib will show clearance of 90% of the BCC. Control subjects will suffer traditional side effects such as muscle tremors, loss of appetite, reduction of smell and taste, and only 50% of the BCCs will resolved in the first 6 months.

[0044] The foregoing description of particular aspect(s) is merely exemplary in nature and is in no way intended to limit the scope of the disclosure, its application, or uses, which may, of course, vary. The materials and processes are described with relation to the non-limiting definitions and terminology included herein. These definitions and terminology are not designed to function as a limitation on the scope or practice of the disclosure, but are presented for illustrative and descriptive purposes only. While the processes or compositions are described as an order of individual steps or using specific materials, it is appreciated that steps or materials may be interchangeable such that the description of the disclosure may include multiple parts or steps arranged in many ways as is readily appreciated by one of skill in the art.

[0045] It will be understood that, although the terms first, second, third, etc. may be used herein to describe various elements, components, regions, and/or layers, these elements, components, regions, and/or layers should not be limited by these terms. These terms are only used to distinguish one element, component, region, or layer from another element, component, region, or layer. Thus, a first element, component, region, or layer, discussed below could be termed a second (or other) element, component, region, or layer without departing from the teachings herein.

[0046] The terminology used herein is for the purpose of describing particular aspects of the disclosure only and is not intended to be limiting. As used herein, the singular forms a, an, and the are intended to include the plural forms, including at least one, unless the content clearly indicates otherwise. Or means and/or. As used herein, the term and/or includes any and all combinations of one or more of the associated listed items. It will be further understood that the terms comprises and/or comprising, or includes and/or including when used in this specification, specify the presence of stated features, regions, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, regions, integers, steps, operations, elements, components, and/or groups thereof. The term or a combination thereof means a combination including at least one of the foregoing elements.

[0047] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. It will be further understood that terms such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and the present disclosure, and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.

[0048] Various modifications of the present disclosure, in addition to those shown and described herein, will be apparent to those skilled in the art of the above description. Such modifications are also intended to fall within the scope of the appended claims.

[0049] Patents, publications, and applications mentioned in the specification are indicative of the levels of those skilled in the art to which the disclosure pertains. These patents, publications, and applications are incorporated herein by reference to the same extent as if each individual patent, publication, or application was specifically and individually incorporated herein by reference.

[0050] The foregoing description is illustrative of particular aspects of the disclosure, but is not meant to be a limitation upon the practice thereof.