Long-acting injectable formulation for use in the treatment and prevention of leishmaniasis in humans and animals

Abstract

The presently disclosed subject matter provides a method and pharmaceutical composition for long-term use in treating or preventing disease conditions caused by Leishmania species parasites such as Leishmaniasis. The pharmaceutical composition is a long-term injectable composition that can include a dose of Itraconazole and a dose of Amiodarone in an amount effective to treat Leishmaniasis, or in an amount effective to prevent Leishmaniasis in a human or animal patient such as a mammal. The pharmaceutical composition may also include a pharmaceutically acceptable vehicle, carrier, or excipient. The long-term method for treating or preventing Leishmania disease is carried out by a single injection of Itraconazole and Amiodarone in an amount effective to treat a subject in need thereof, and / or in an amount effective to prevent the subject from contracting the disease so that repeated dosages are not required again for a long-term period such as 6 or 12 months. The present compositions, methods, and uses are safer and longer lasting, more patient friendly, and provide a safer and more effective way of treating or preventing Leishmaniasis than previously possible.

Description

[0001] LONG-ACTING INJECTABLE FORMULATION FOR USE IN THE TREATMENT AND PREVENTION OF LEISHMANIASIS IN HUMANS AND ANIMALS CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of US Provisional Application Ser. No. 63 / 640,960 filed May 1, 2024, the disclosure of said application being incorporated herein in its entirety. FIELD The presently disclosed subject matter relates to a pharmaceutical composition and method used for providing long-term treatment and prevention of the parasitic diseases known as Leishmaniasis in humans and animals. More particularly, the presently disclosed subject matter relates to a long-term injectable or implantable pharmaceutical composition comprising a dose of Itraconazole and a dose of Amiodarone in amounts suitable to allow long-term treatment or prevention of the parasitic disease Leishmaniasis, a method of preparing the injectable pharmaceutical composition to allow it to be administered by injection for use in long-term treatment and prevention of disease conditions caused by species of the genus Leishmania, and a method of administering this pharmaceutical composition so that it may be used in the long-term treatment and prophylaxis of Leishmaniasis in human and animal patients. BACKGROUND Leishmaniasis is a parasitic disease that has severe effects on humans and animals throughout the world. This disease primarily affects canines, felines, and humans is found in parts of the tropics, subtropics, and southern Europe, and it is classified as a neglected tropical disease (or NTD). Leishmaniasis is caused by infection with Leishmania parasites, which are spread by the bite of insects such as phlebotomine sand flies. In one mode of transmission, sand flies become infected by sucking blood from an infected animal or person. Some types of Leishmania parasites also may be spread via contaminated needles (needle sharing), blood transfusions, or even congenital transmission from a pregnant woman to her baby. There are thus multiple modes of transmission that can cause the spread of this condition to many parts of the World. The number of new cases may vary or change over time and are difficult to estimate, but it is estimated that there are over a million new cases of Leishmaniasis per year. In the Eastern Hemisphere, Leishmaniasis is found in some parts of Asia, the Middle East, Africa (particularly in the tropical region and North Africa, with some cases elsewhere), and southern Europe. It is not found in Australia or the Pacific Islands. In the Western Hemisphere. leishmaniasis is found in some parts of Mexico, Central America, South America, and North America. In the US, incidents of leishmaniasis have been reported in Oklahoma and Texas, and many cases have arisen in U.S. civilian travelers that were acquired in common tourist destinations in Latin America, such as in Costa Rica. U.S. military personnel have become infected in various countries, such as Iraq and Afghanistan. There are several different forms of leishmaniasis in people. The most common forms are cutaneous leishmaniasis, which causes skin sores, and visceral leishmaniasis, which affects several internal organs (usually spleen, liver, and bone marrow). Still other forms of diseases caused by Leishmania include subcutaneous Leishmaniasis and mucocutaneous Leishmaniasis. Despite the growing interest in the development of new drugs for treatment, current therapies for Leishmania disease remain unsatisfactory. Previously, a combination of amiodarone and itraconazole was used in the treatment of Chagas disease as set forth in US Patent No.10,736,891 (Madigan et al.), but a reported attempt to use this technology in Leishmania amazonensis did not result in a successful treatment regimen (see Anversa et al., Int’l Journal of Antimicrobial Agents, 50:159-165, 2017). However, it appears this treatment failed because the authors of the article used a compounded form of itraconazole prepared using a dilution and ultrasonic bath which limited its effects. In addition, therapeutic levels of both itraconazole and amiodarone in the subject’s plasma were not monitored, and the itraconazole was not treated so as to make it more bioavailable. It thus appears that the treated animals only absorbed a sub-therapeutic and non-bioavailable amount which led to the erroneous conclusion that such a combination could not be made to work against Leishmania amazonensis. Further, it has also been difficult to develop proper methods and compositions that allow for safe and effective treatment of and protection from Leishmaniasis, namely one that is patient-friendly so as to improve the chances that such a formulation can be used on an infected human or pet will be effective over a longer term. Current medications have not been designed to be easy to administer and effective over a longer-term period such as six months or a year. Another issue is the possibility of side effects which may include cardiovascular problems or other harmful conditions such as ventricular arrythmias which can be extremely debilitating or even fatal. Another problem that has held back efforts to develop successful long-term treatment and prevention of Leishmaniasis is that it was generally thought that a long- acting injectable dosage form was not possible because of the solubility profiles for amiodarone and itraconazole. Even further, it was also thought that such long-term treatment would necessarily require high doses of the active ingredients and a large volume of fluid to be delivered to patient tissues. Accordingly, despite previous attempts to combine itraconazole and amiodarone in parasitic treatments, there is still a need to develop a method that can be used to provide long-term treatment and prevention of Leishmaniasis patients in a manner that is safe and effective for long periods of time, and is also user-friendly so as to increase the likelihood that the patient will timely receive the required dose of the medication. As a result, the present inventors have developed a new system and method whereby a safe and effective long-term injectable composition for use in treating and / or preventing Leishmaniasis in human and animal patients is provided which overcomes prior issues, maximizes the likelihood that a patient will receive a proper dose of medication that will cover a longer period of time, and at the same time also minimizes the risk of undesirable side effects. SUMMARY In accordance with the present invention, the presently disclosed subject matter provides an injectable pharmaceutical composition use in long-term methods of treating and / or preventing disease conditions caused by parasites of the genus Leishmania, otherwise known as Leishmania disease or Leishmaniasis. The present invention provides a pharmaceutical drug therapy that is a long-acting treatment and preventative parasiticide against species of parasites from the genus Leishmania, and thus composition and method allows for a one-time treatment that is effective for up to one year or longer. The pharmaceutical composition of the invention is a long-term injectable composition that can include a dose of Itraconazole and a dose of Amiodarone in an amount effective to treat Leishmaniasis, or in an amount effective to prevent Leishmaniasis in a human or animal patient such as a mammal. The pharmaceutical composition may also include a pharmaceutically acceptable vehicle, carrier, or excipient. The long-term method for treating or preventing Leishmaniasis is carried out by one or two injections of Itraconazole and Amiodarone in an amount effective to treat a subject in need thereof, and / or in an amount effective to prevent the subject from contracting the disease so that repeated dosages are not required again for a long-term period such as 3, 6, or 12 months. Accordingly, the long-term method of the invention may have a range of treatment or prophylaxis that has a duration of anywhere from 3 months to 1 year or longer. The present compositions, methods, and uses are safer and longer lasting, more patient friendly so as to increase the likelihood of patient compliance, and provide a more effective way of treating or preventing Leishmaniasis than previously possible. The present invention provides a pharmaceutical composition and form that improves upon the oral dosage form, and which is administered in the form of an injectable composition, such as in the form of a subcutaneous injection, an intramuscular injection, and / or implantable device. This injectable therapeutic composition allows for long-term treatment and prevention of Leishmaniasis in humans and animals, and in particular in mammals. The invention provides a method and composition for treatment or prevention that is long-lasting, but is carried out in such a manner that the overall length of therapy is significantly shorter than previous modes, and more patient friendly since it avoids the need for a continuous dosage regimen over a long period of time. As indicated herein, the present invention overcomes previous issues and concerns relating to the use of a combination of amiodarone and itraconazole because it has been difficult to develop a particularly suitable form of administration that could be used to provide long-term care in treating and preventing Leishmaniasis. As indicated above, these active ingredients have sometimes been associated with undesirable side effects such as cardiovascular problems or arrhythmias. The present invention resulted from an attempt to improve the safety profile and long-term effectiveness of treatments that involved oral dosage forms. In particular, the ability to improve the safety profile by potentially administering significantly lower doses of each active ingredient was examined in terms of the relative bioavailability of an oral dosage form in comparison to a long-acting injectable dosage form. The present inventors thus discovered that this particular drug combination could be administered for long-term treatment or prevention of Leishmaniasis in lower doses and for a significantly shorter period of time when in a suitable injectable form, such as a subcutaneous injection, an intramuscular injection, and / or implantable device at proper levels of the active ingredients. The present injectable form further enhances safety and effectiveness because it overcomes issues of dosing compliance, drug resistance, reinfection and reluctance of companion animal owners to take responsibility for long-term daily dosing of the animal in need of treatment. As a result, the present long-term injectable system, method, and compositions also provides economic benefits because it lowers numbers of necessary treatments or administrations, and thus can be provided at a much lower costs than previous treatment compositions and methods of parasites such as those that cause Leishmaniasis. In one exemplary embodiment, an injectable long-term pharmaceutical composition is provided which has a lower dose of active ingredients compared to the oral dosage forms and is designed to deliver and maintain therapeutic blood levels of amiodarone and itraconazole in the blood of a patient or subject. In certain embodiments, a method of treating Leishmaniasis is provided wherein the dosage of the pharmaceutical composition of the invention is designed to result in sufficient therapeutic and biologically available amounts of Amiodarone and Itraconazole in the patient, and in one exemplary embodiment, a pharmaceutical composition is provided that contains a dosage of Amiodarone in an amount oi approximately from about 3.5 mg / kg to about 5.5 mg / kg of the subject or patient to be treated, and in another embodiment the desired range may be around 4.0 to around 5.0 mg / kg of the patient being treated. In the pharmaceutical composition of the invention, an amount of Itraconazole is also administered to the patient, and this may be in the range of approximately 2.0 mg / kg to about 8.0 mg / kg of the subject or the patient being treated, and in another embodiment this amount may be in the range of about 2.5 mg / kg to about 7.5 mg / kg of the subject or patient. It is possible to employ the active ingredients of the invention so that they are delivered in a single vial or pre-filled syringe containing both active ingredients of amiodarone and itraconazole. In an exemplary embodiment of the method of the invention, a long-term treatment can be obtained by delivering the injection to the human or animal patient in such a manner so that another injection is not needed for a multi-month period. For example, it is possible to deliver the long-term injectable pharmaceutical composition of the invention once every one and a half months so that the treatment regimen is a total of three months, but any additional treatment would not need to be given again for another year. In another exemplary embodiment, the method of long-term treatment of Leishmaniasis using the injectable composition of the invention as described herein can also have a pre-treatment period wherein the subject is provided with a conventional treatment with a tablet comprising a combination of Amiodarone and Itraconazole. In an exemplary embodiment, the tablet will have a higher dosage of the active ingredients than as described herein for the present invention. For example, the tablet when used in canine treatment may have a dosage of about 50 mg of Itraconazole and about 75 mg of Amiodarone, and when used in feline treatment, the tablet may have a dosage of about 25 mg Itraconazole and about 37.5 mg of Amiodarone. These tablets may contain Itraconazole that is prepared using a hot melt extrusion (HME) process that would be known to those skilled in the art. Such a pretreatment step may be for a period of up to about one month. Following the completion of the pre-treatment dosage regiment, the long-term injectable composition of the invention may then be administered to the subject or patient as described herein. In one suitable example, following the 30-day or month-long treatment with the tablets, either one or two long-acting injections of the pharmaceutical composition of the invention described herein can be administered to the patient for a total treatment period of one year. The present composition and method thus is able to administer a one-year treatment over the course of three months, and this is an improvement upon previous regimens of the active ingredients which must be taken regularly over the course of a year. The present composition and method thus is able to administer a one-year treatment over the course of three months, and this is an improvement upon previous regimens of the active ingredients which must be taken regularly over the course of a year. Alternatively, another long-term method of administration using the injectable composition as described herein can comprise the delivery of the active ingredients in a single vial or pre-filled syringe containing both amiodarone and itraconazole actives delivered as a single injection which will then not need to be given again for another 12 months or longer. Such a treatment is effective against Leishmaniasis, long-lasting, and provide economic benefits because costs for the treatment for one year are significantly lower than other treatments that must be regularly given over the course of many months or a year. In accordance with the invention, a long-term injectable prophylactic formulation is also provided which contains an alternate dosage regimen designed to ensure protection against Leishmaniasis for an extended long-term period of from a few months to a year or longer. In one embodiment of the long-tern prophylactic therapy in accordance with the invention, Itraconazole and Amiodarone are administered in a long-term injectable form, but with generally lower amounts than the dosages above for long-term treatment methods. In one embodiment, the dosage may be around one-third of the dosage of the active ingredients when compared to the method of treatment as described hereinabove. This injectable composition is designed to deliver and maintain therapeutic blood levels of Itraconazole and amiodarone via a one-time or two-time dose that is protective for multiple months and up to one year or greater. In an exemplary embodiment, an injectable formulation is prepared containing approximately 0.5 to 5.5 mg / kg of Itraconazole per subject or patient and approximately 0.5 to 5.5 mg / kg of Amiodarone per subject or patient being administered the active ingredients. In another embodiment, the amount of Itraconazole administered may be in the range of from about 1.0 to about 5.0 mg / kg of a patient or subject, and the Amiodarone can be administered in an amount of from about 1.0 -5 mg / kg of the patient or subject. This dosage can be provided in any suitable injectable or implantable form such as a single vial or pre-filled syringe, but also can be administered separately at the same time. In an exemplary method of protecting a subject or patient against Leishmaniasis, the two active ingredients of Amiodarone and Itraconazole may be delivered in a single vial or pre-filled syringe or other implantable form designed to be administered once every six months, or two injections a year, and thus the protection from the present injectable composition will be for 12 months or longer. In another exemplary embodiment, the two active ingredients may be administered only once every 12 months for a total of one injection per year, and this method may be administered again when needed so as maintain protection against Leishmaniasis for a multi-year period. In one embodiment, injectable forms can be prepared by forming micro- encapsulation matrices of the active ingredients in biodegradable polymers such as polylactide-polyglycolides, poly(orthoesters), and / or poly(anhydrides). Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Injectable formulations may also be prepared by entrapping the active ingredients in liposomes or microemulsions, which are very compatible with body tissues. The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable media just prior to use. The formulation may also be sterilized via terminal sterilization processes including but not limited to Steam, Ethylene Oxide treatment, and Radiation. The formulations can also be prepared using suitable pharmaceutically acceptable vehicles, carriers or excipients, and in one suitable form, an inert carrier can be used which includes sugars such as lactose. In another embodiment, drug formulations may be prepared that utilize a two-vial system, and in an exemplary embodiment, one vial may contain itraconazole in a range from 1-50 mg and amiodarone in a range from 1.5-75 mg. In exemplary embodiments, the active ingredients as used with a suitable and pharmaceutically acceptable vehicle, carrier or excipient. In some embodiments, other ingredients in the formulation in that vial may include poly-dl-lactide-co-glycolide, such as in amounts of 1-170 mg, mannitol USP, such as in amounts of 1-85 mg, carboxymethylcellulose sodium USP, such as in amounts of 1- 30 mg, and polysorbate 80 NF, such as in amounts of 1-2 mg . A second vial may contain 2 mL sterile water for injection to be added to the first vial. In another exemplary embodiment of the invention, a single pre-filled syringe containing both active ingredients is used in the method of treatment of and protection against Leishmaniasis. In yet another embodiment, two separate long-acting injectable formulations for Itraconazole and Amiodarone are dosed at the same time, or a multi-use vial at various fixed concentrations can be volumetrically adjusted to obtain the proper dose for patients of varying weights in order to achieve maximally effective therapeutic doses to provide the adequate blood levels of amiodarone and itraconazole in the patient. In another embodiment, the dosage form may include a two vial system whereby one vial contains the lyophilized formulation containing active and inactive ingredients and the second vial contains water for reconstitution. Another formulation for subcutaneous administration would be a pre-filled, multi-dose, adjustable syringe. Another may be a drug eluting titanium implant for localized drug delivery. As set forth herein, the present invention is advantageous because it provides a prophylactic dosage which allows the patient to substantially reduce or eliminate the risk of infection and disease caused by a parasite of the species Leishmania. This prophylactic method thus also substantially lowers or eliminates the risk for sever hepatic, kidney, and lymphatic system damage associated with chronic Leishmaniasis. In addition, the present injectable composition and method will also protect the patient against possible death that would be associated with acute and chronic L. Infantum infections. The present invention thus provides a prophylactic therapy that can be administered in even lower doses than either current oral or injectable treatment formulations, and the present invention allows for a period of treatment that has a significantly shorter period of time than current therapies, which even further enhances the drug combination safety profile. With regard to the treatment of the invention, this also allows for improving safety over the current oral dosage forms in that the present compositions will be administered at lower doses of each active ingredient because of the improved bioavailability of the present injectable form when compared with a form used in an oral dosage. The long-acting injectable pharmaceutical dosage form of the present invention when used for treating or preventing Leishmaniasis thus an improvement over current and previous forms of treatment or prevention because it can (1) overcome potential issues related to dosing compliance by the administration of either a bi-annual or annual injection to be done by the veterinarian; (2) avoid creating a drug resistance issue by ensuring long term therapy without interruption; (3) prevents against reinfection over a long period of time following the initial dose; (4) overcome the normal reluctance of companion animal owners to take responsibility for long-term daily dosing; (5) which results in significant economic benefits to the pet owner or patient because it involves a much lower use of the active ingredients that is effective for period of up to a year or longer. The long-term injectable pharmaceutical compositions for use in treating or preventing Leishmaniasis in accordance with the invention comprises as active ingredients a dose of Itraconazole and a dose of Amiodarone, and in certain embodiments, the active ingredients can be in the form of a pharmaceutical composition that includes the active ingredient in a pharmaceutically acceptable carrier. In further embodiments, the pharmaceutical composition for use in long-term treatment or prevention of Leishmaniasis may also include a second pharmaceutically acceptable carrier. In some embodiments, the presently disclosed subject matter provides that the dose of Itraconazole is first mixed with the second pharmaceutically acceptable carrier. In certain exemplary embodiments, the dosage of the active ingredients can be provided in a single vial, or they can also be administered simultaneously or separately to the patient. In general, the dosage should be provided at a level which results in suitable levels of the active ingredients in the blood stream of the patient. For example, the compositions of the invention should be sufficient to result in a plasma concentration in the patient of about 0.1 to 3.0 "g / ml of the active ingredients, or in another embodiment from about 0.3 to 2.0 "g / ml of the active ingredients. Still further, in another embodiment of the present invention, the long-term injectable pharmaceutical composition may have a dosage sufficient to result in a plasma concentration in the patient of from about 0.1 to about 3.0 "g / ml of Itraconazole, or from about 0.2 to about 3.0 "g / ml of Itraconazole. The dosage of Itraconazole may also be sufficient to provide a plasma concentration in the patient of at least 0.5 mcg / mL Itraconazole, or at least 1.0 mcg / mL Itraconazole. With regard to Amiodarone, in one embodiment, the levels of Amiodarone in the long-term injectable pharmaceutical composition of the invention are sufficient to result in a plasma concentration in the patient of from about 0.1 to about 3.0 "g / ml, or from about 1.5 to about 2.5 "g / ml in the patient. . In additional embodiments, pharmaceutical compositions containing the active ingredients of the long-term injectables of the invention are designed to have suitable bioavailability in the blood stream of the patient so to provide effective long-term treatment or prevention of Leishmaniasis as described herein. In accordance with the invention, a method for use in the long-term treatment of Leishmaniasis in a human or animal subject in need thereof is provided that comprises administering to said subject a long-term injectable composition comprising Amiodarone in the range of from about 3.5 mg / kg to about 5.5 mg / kg of the subject, and Itraconazole in the range of from about 2.0 mg / kg to about 8.0 mg / kg of the subject. These active ingredients may be administered along with a pharmaceutically acceptable vehicle, carrier, or excipient of such types that are well known in the art and used in many pharmaceutical compositions. In one embodiment of the inventive method, the Itraconazole and Amiodarone are administered together, or alternatively, the Itraconazole and Amiodarone may be are administered separately to the patient or subject. In another embodiment, the dosage of Amiodarone in the injectable composition may be in the range of from about 4.0 mg / kg to about 5.0 mg / kg of the subject, and the dose of Itraconazole may be in the range of from about 2.5 mg / kg to about 7.5 mg / kg of the subject. The method of treatment is designed so that only one or two injections are required to treat the patient for a long-term period of up to a year or longer. In the embodiments wherein two injections are employed, there is a long period following the first injection before a second injection needs to be administered. In certain embodiments, the second injection is administered one and a half months or three months after the first injection, and then no additional injections will be needed for at least one year or longer. In this embodiment, the treatment period will thus be two injectable shots one and a half months apart, and this treatment will be effective for up to a year or longer. In cases wherein the treatment is successful and the Leishmaniasis has cleared, no additional treatment will be needed. In other embodiments of the method of the present invention, longer periods between the initial dose and the second dose may be provided. For example, it is possible to administer the first injection and then not administer the second injection for a period of three months or six months, or any period in between these two time frames. In both cases, the treatment regimen will be only two injections that will provide effective treatment for one year or longer. In an another embodiment, a one-time dosage of the injectable composition as described above is provided and then not administered for at least 12 months. In such a method, there is only a single injection that will provide effective treatment of Leishmaniasis for one year or longer. As indicated above, the injectable form for containing the active ingredients of the invention may be any suitable injectable form such as a form of a subcutaneous injection or a muscular injection, or as indicated above, the term injectable includes the use of an implantable device which may be implanted into the patient Implantable drug delivery systems (sometimes referred to as IDDSs) provide a variety of ways of implanting an active drug into a patient, and such systems and devices may be bioengineered and then surgically placed inside the patient's tissues where needed to obtain the maximum effect of the active ingredients inside the patient. Such imputable devices can be used advantageously because they can avoid problems such as first-pass metabolism, and they can also reduce the systemic toxicity of the drug by having the active ingredients released only in the vicinity of target tissues when needed. In an exemplary embodiment of the present method, the dose of Amiodarone and Itraconazole is sufficient to result in an effective amount of these active ingredients in the patient. In one embodiment of the present method, the dose of Amiodarone and Itraconazole is sufficient to result in a plasma concentration in the patient of from about 0.1 to about 3.0 "g / ml of the active ingredients. In other embodiments, the dose is sufficient to result in a plasma concentration in the patient of from about 0.3 to about 2.0 "g / ml of the active ingredients. In other embodiments of the method, the injectable pharmaceutical composition used in this method may have a dosage sufficient to result in a plasma concentration of from about 0.1 to about 3.0 "g / ml of Itraconazole in the patient, or from about 0.2 to about 3.0 "g / ml of Itraconazole in the patient. In certain embodiments, the dosage of Itraconazole may also be sufficient to provide a plasma concentration in the patient of at least 0.5 mcg / mL Itraconazole, or at minimum 1.0 mcg / mL of Itraconazole. With regard to Amiodarone, in one embodiment, the levels of Amiodarone in the long-term injectable pharmaceutical composition used in thus method will be sufficient to result in a plasma concentration of from about 0.1 to about 3.0 "g / ml Amiodarone in the patient, or from about 1.5 to about 2.5 "g / ml Amiodarone in the patient. In certain embodiments, the total dose of Itraconazole in the injectable forms of the invention may be from about 1 mg to about 50 mg; and the dose of Amiodarone in such forms may be from about 1.5 mg to about 75 mg. In certain treatment regimens, the patient may be provided with food at or around the time of the injections. In accordance with the invention, a method for use in the long-term prevention of Leishmaniasis in a human or animal subject in need thereof is also provided that comprises administering to said subject a long-term injectable composition comprising Amiodarone in the range of from about 0.5 mg / kg to about 5.5 mg / kg of the subject, and Itraconazole in the range of from about 0.5 mg / kg to about 5.5 mg / kg of the subject. These active ingredients may be administered along with a pharmaceutically acceptable vehicle, carrier, or excipient of such types that are well known in the art and used in many pharmaceutical compositions. In one embodiment of the inventive method, the Itraconazole and Amiodarone are administered together, or alternatively, the Itraconazole and Amiodarone may be are administered separately to the patient or subject. In another embodiment, the dosage of Itraconazole may be in the range of from about 1.0 mg / kg to about 5.0 mg / kg of the subject, and the dosage of Amiodarone is in the range of from about 1.0 mg / kg to about 5.0 mg / kg of the subject. The method of prophylaxis is designed so that only one or two injections are required to treat the patient for a long-term period of up to a year or longer. In the embodiments wherein two injections are employed, there is a long period following the first injection before a second injection needs to be administered. In certain embodiments, the second injection is administered three months after the first injection, and then no additional injections will be needed to provide protection against Leishmaniasis for at least one year or longer. In this embodiment, the full extent of the prophylaxis regimen will thus be two injectable shots three months apart, and this treatment will be effective for up to a year or longer. Additional injections in accordance with the invention may take place as needed following the initial 12 months. In other embodiments of the method of prophylaxis of the present invention, longer periods between the initial dose and the second dose may be provided. For example, it is possible to administer the first injection and then not administer the second injection for a period of six months. In both cases, the regimen will be only two injections that will provide effective protection against Leishmaniasis for one year or longer. In an another embodiment, a one-time dosage of the injectable composition as described above is provided and then not administered for at least 12 months. In such a method, there is only a single injection that will provide effective prevention of Leishmaniasis for one year or longer. As indicated above, the injectable form for containing the active ingredients of the invention for use in the prophylactic method may be any suitable injectable form such as a form of a subcutaneous injection or a muscular injection, or as indicated above, the term injectable includes the use of an implantable device which may be implanted into the patient Implantable drug delivery systems (or IDDSs) as described above may also be utilized. In an exemplary embodiment of the present prophylactic method, the dose of Amiodarone and Itraconazole is sufficient to result in an effective amount of these active ingredients in the patient. In one embodiment of the present method, the dose of Amiodarone and Itraconazole is sufficient to result in a plasma concentration in the patient of from about 0.1 to about 3.0 "g / ml of the active ingredients. In other embodiments, the dose is sufficient to result in a plasma concentration in the patient of from about 0.3 to about 2.0 "g / ml of the active ingredients. In other embodiments of the prophylactic method, the injectable pharmaceutical composition used in this method may have a dosage sufficient to result in a plasmaconcentration of from about 0.1 to about 3.0 μg / ml of Itraconazole in the patient, or fromabout 0.2 to about 3.0 μg / ml of Itraconazole in the patient. In certain embodiments, thedosage of Itraconazole may also be sufficient to provide a plasma concentration in the patient of at least 0.5 mcg / mL Itraconazole, or at minimum 1.0 mcg / mL of Itraconazole. With regard to Amiodarone, in one embodiment, the levels of Amiodarone in the long-term injectable pharmaceutical composition used in thus method will be sufficient to result in aplasma concentration of from about 0.1 to about 3.0 μg / ml Amiodarone in the patient, orfrom about 1.5 to about 2.5 μg / ml Amiodarone in the patient. In certain embodiments, the total dose of Itraconazole in the injectable forms used for prophylaxis against leishmaniasis may be from about 1 mg to about 50 mg; and the dose of Amiodarone in such forms may be from about 1.5 mg to about 75 mg. As indicated above, the prophylactic injectable composition used in the present method may be in any suitable form that can be safely injected into a patient, such as a subcutaneous injection, a muscular injection, or an implantable device. In another embodiment of the invention, a long-term injectable pharmaceutical composition for use in long-term treatment of Leishmaniasis is provided which comprises a dose of Amiodarone in an amount of from about 3.5 mg / kg to about 5.5 mg / kg of the subject, a dose of Itraconazole in an amount of from about 2.0 mg / kg to about 8.0 mg / kg of the subject; and a pharmaceutically acceptable carrier. In an alternate embodiment, the long-term injectable pharmaceutical composition for use in long-term treatment of Leishmaniasis may include a dose of Amiodarone in the range of about 4.0 mg / kg to about 5.0 mg / kg, and a dose of Itraconazole in the range of about 2.5 mg / kg to about 7.5 mg / kg. The injectable composition may be in the form of a single vial or container containing both of the active ingredients, and in still other injectable forms, the Itraconazole and Amiodarone may be provided to the patient in separate vials or containers. The long-term injectable pharmaceutical composition for treatment of Leishmaniasis may be designed so that dose is sufficient to result in a plasma concentration in the patient of from about 0.1 to3.0 μg / ml of the active ingredients, or from about 0.3 to about 2.0 μg / ml of the activeingredients. A method for treating Leishmaniasis in a human or animal subject in need thereof that comprises administering to the subject an effective amount of this long-term pharmaceutical composition. In another embodiment, a long-term injectable pharmaceutical composition for use in long-term prevention of Leishmaniasis is provided which comprises a dose of Amiodarone in an amount of from about 0.5 mg / kg to about 5.5 mg / kg of the subject, a dose of Itraconazole in an amount of from about 0.5 mg / kg to about 5.5 mg / kg of the subject; and a pharmaceutically acceptable carrier. In an alternate embodiment, the long- term injectable pharmaceutical composition for use in long-term treatment of Leishmaniasis may include a dose of Amiodarone in the range of about 1.0 mg / kg to about 5.0 mg / kg, and a dose of Itraconazole in the range of about 1.0 mg / kg to about 5.0 mg / kg. In general, the long-term injectable pharmaceutical composition may be in the form of a single vial or a pre-filled syringe. The injectable composition may be in the form of a single vial or container containing both of the active ingredients, and in still other injectable forms, the Itraconazole and Amiodarone may be provided to the patient in separate vials or containers. The long-term injectable pharmaceutical composition for prevention of Leishmaniasis may be designed so that dose is sufficient to result in a plasmaconcentration in the patient of from about 0.1 to 3.0 μg / ml of the active ingredients, or fromabout 0.3 to about 2.0 μg / ml of the active ingredients. A method for preventingLeishmaniasis in a human or animal subject in need thereof that comprises administering to the subject an effective amount of this long-term pharmaceutical composition. As indicated above, the methods of the invention may be used to achieve long-term treatment or prevention of Leishmaniasis in human or animal subjects in need thereof. In certain embodiments, the subject may be a mammal, and the mammal may be selected from the group consisting of a human, a dog, a cat, a monkey, or other mammal that might be domesticated or retained in preserves or in zoos, and the subject may be a pet. ` Still further, a use of itraconazole and amiodarone for the manufacture of a medicament for the long-term treatment of Leishmaniasis in a human or animal subject in need thereof is provided, and this medicament may be a pharmaceutical composition having a dose of itraconazole in the range of about 2.5 mg / kg to about 7.5 mg / kg of a subject, and a dose of amiodarone in the range of about 4.0 mg / kg to about 5.0 mg / kg of the subject. ` In another embodiment, a use of itraconazole and amiodarone for the manufacture of a medicament for the long-term prevention of Leishmaniasis in a human or animal subject in need thereof is provided, and this medicament may be a pharmaceutical composition having a dose of itraconazole in the range of about 1.0 mg / kg to about 5.0 mg / kg of a subject, and a dose of amiodarone in the range of about 1.0 mg / kg to about 5.0 mg / kg of the subject. In certain embodiments, the subject or patient treated by the Itraconazole and Amiodarone may be a human or animal patient. In other embodiments, the subject or patient may be a mammal, and may also be selected from the group consisting of a human, a dog, a cat, and a monkey. In other exemplary embodiments, the current invention is a combination long-acting subcutaneous injection containing both itraconazole and amiodarone in a single injection. In addition, this combination is prepared using an actual micelle formulation with percentages of inactive ingredients, e.g., Glycerol and BHT (Butylated hydroxytoluene). As set forth herein, the present invention also comprises a provides a formulation for a companion diluent formulation which is embodied in a two-vial system wherein one vial contains lyophilized micelles encapsulating the active combination of itraconazole and amiodarone as active ingredients and wherein the second vial contains a diluent which is then combined with the lyophilized micelles to create the final product. As shown herein, the in-vitro dissolution data described below supports a release profile of at least approximately 6 months. Still further, the method of the invention also contains an end-terminal sterilization step, and the examples provided below provides stability data showing the formulations of this disclosure are stable before and after sterilization at room temperature. A pH range for our formulation is also provided. The present invention thus provides a substantial advantage over prior art methods and compositions because it allows for a long-acting subcutaneous dosage for that offer protection against Leishmaniasis, and this method can be accompanied by a short-acting intravenous injection of itraconazole and amiodarone as a loading dose prior to or in conjunction with the long-acting subcutaneous dosage form. As described further below, Applicant herein describes several embodiments of the presently-disclosed subject matter, and, in many cases, lists variations and permutations of these embodiments. This disclosure is thus merely exemplary of the numerous and varied embodiments falling with the present invention. The recitation of one or more representative features of a given embodiment is likewise exemplary. Such an embodiment can typically exist with or without the feature(s) mentioned; likewise, and those features can be applied to other embodiments of the presently-disclosed subject matter, whether listed or not. To avoid excessive repetition, this section does not list or suggest all possible combinations of such features. Advantages of the presently-disclosed subject matter will become evident to those of ordinary skill in the art after a study of the description, and non-limiting Examples as set forth herein. BRIEF DESCRIPTION OF DRAWING FIGURES Fig.1 shows a schematic of an exemplary embodiment of the method and apparatus of the present disclosure. Fig.2 shows the dissolution profiles of Amiodarone HCl and Itraconazole contained in the T1S sterilized formulation. Fig.3 shows the dissolution profiles of Amiodarone HCl and Itraconazole contained in the T3S sterilized formulation. DESCRIPTION OF EXEMPLARY EMBODIMENTS The details of one or more exemplary non-limiting embodiments of the presently- disclosed subject matter are set forth herein. Modifications to embodiments described herein and other embodiments will be evident to those of ordinary skill in the art after a study of the information provided in this document. The information provided in this document, and particularly the specific details of the exemplary embodiments as described, is provided primarily for clearness of understanding and no unnecessary limitations are to be understood therefrom. While the terms used herein are believed to be well-understood by one of ordinary skill in the art, definitions are set forth to facilitate explanation of the presently-disclosed subject matter. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the presently-disclosed subject matter belongs. Although a number of methods, devices, and materials similar or equivalent to those described herein may be used in the practice or testing of the presently-disclosed subject matter, representative methods, devices, and materials are now described. Following long-standing patent law convention, the terms “a,” “an,” and “the” refer to “one or more” when used in this application, including the claims. Thus, for example, reference to “a subject” includes a plurality of such subjects, and so forth. Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in this specification and claims are approximations that can vary depending upon the desired properties sought to be obtained by the presently-disclosed subject matter. As used herein, the term “about,” when referring to a value or to an amount of mass, weight, time, volume, concentration or percentage is meant to encompass variations of in some embodiments ±20%, in some embodiments ±10%, in some embodiments ±5%, in some embodiments ±1%, in some embodiments ±0.5%, and in some embodiments ±0.1% from the specified amount, as such variations are appropriate to perform the disclosed method. In addition, when used herein, if a range is indicated, any specific amount within that range is considered part of the invention. For example, wherein a range is given in mg / kg, this means that the range includes any individual amount within the range, for example is a range is provided as “2.0 to 8.0 mg / ml” all ranges within the parameter of that range are considered disclosed, and the range covers all individual amounts within that range, e.g., in 0.1 or 0.5 intervals. Accordingly, the inclusive range of “2.0 to 8.0” would include, for example, each 0.1 interval, such that the range would include a lower limit of about 2.1, 2.2, 2.3, etc. in addition to about 2.0, and the upper range would include an upper limit of 7.9, 7.8, 7.7, etc., in addition to about 8.0. This would apply to all such ranges herein, in whatever units or measures of time are used. Accordingly, the specific amount used may include any specific amount in the range, such as in 0.1 mg.kg increments, so that amounts of 2.0, 2.1, 2.2, 2.3 and so forth up and including through 8.0 could be administered within the range of from about 2 / 0 to about 8.0, and similarly for all ranges in accordance with the present invention. As also used herein, the present subject matter provides an injectable composition containing a dosage of the active ingredients Itraconazole and Amiodarone in amounts effective for the long-term treatment or prevention of leishmaniasis in human or animal patients. As indicated above, the amounts used in the present compositions and methods have a range, such as the ranges for both Itraconazole and Amiodarone, whether taken simultaneously in a single pharmaceutical form or administered separately. In these ranges, it is contemplated that the range covers any range that falls within the extent of the range. For example, the dosages may include every 0.5 mg / kg interval within said range, for example, a range of from about 2.0 to about 8.0 would include specific dosages such as about 2.0 mg / kg, about 2.5 mg / kg, about 3.0 mg / kg, about 3.5 mg / kg, and so forth up to and including about 8.0 mg / kg. Further, the disclosed ranges include every range included within a larger range, such that an exemplary range of about 2.0 to 8.0 would include ranges of about 2.0 and 7.5, between about 2.5 and 8.0, between about 2.5 and 7.5, and so forth through the entire range, including the upper and lower amounts in said range. The presently disclosed subject matter relates to an injectable pharmaceutical composition for use in treating Leishmania disease, methods of treatment thereof, and methods of producing the injectable formulation containing the active ingredients and pharmaceutical compositions containing said active ingredients. Such injectable compositions can take the form of any suitable vehicle by which the active ingredients can be injected or implanted into a human or animal patient, such as a subcutaneous injection, an intramuscular injection, and / or implantable device, and thus the reference herein to “injectable” covers all forms wherein the active ingredients are provided in an injectable or implantable manner. In one exemplary embodiment, the presently disclosed subject matter relates to an injectable composition and a method for use in long-term treatment of Leishmaniasis in humans and animals comprising a dose of Itraconazole and a dose of Amiodarone. In another exemplary embodiment, the presently disclosed subject matter relates to an injectable composition and a method for use in long-term prevention of Leishmaniasis in humans and animals comprising a dose of Itraconazole and a dose of Amiodarone. The pharmaceutical composition of the invention is a long-term injectable composition that can include a dose of Itraconazole and a dose of Amiodarone in an amount effective to treat Leishmaniasis, or in an amount effective to prevent Leishmaniasis in a human or animal patient such as a mammal. The pharmaceutical composition may also include a pharmaceutically acceptable vehicle, carrier, or excipient. As used herein, the term “pharmaceutical vehicle, carrier or excipient” or “pharmaceutically acceptable vehicle, carrier or excipient” may refer to any of a wide variety of materials known for general usage in delivering a pharmaceutical agent or agents to a patient. Non- limiting examples of such materials include any solid forms that can be utilized in an injectable or implantable composition, and may also may include sterile aqueous or non- aqueous solutions, dispersions, suspensions or emulsions, as well as sterile powders for reconstitution into sterile injectable solutions or dispersions just prior to use. In additional embodiments, when needed, fluidity of an injectable solution can be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants when needed. The injectable compositions of the invention can also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Other additives such as those preventing undesirable effects of other microorganisms may include various antibacterial and antifungal agents such as paraben, chlorobutanol, phenol, sorbic acid and the like. Other isotonic agents such as sugars, sodium chloride and the like may be used in the composition where suitable. Prolonged absorption of the injectable pharmaceutical form can be brought about by the inclusion of agents, such as aluminum monostearate and gelatin, which delay absorption. Injectable depot forms can be provided by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide, poly(orthoesters) and poly(anhydrides). Drug release amount and location may also be controlled by virtue of the particular polymer employed in the injectable form, and injectable formulations may be formed by entrapping the drug in materials such as liposomes or microemulsions which are in a form compatible with body tissues. The injectable formulations can be sterilized, e.g., by filtration through a bacterial-retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable media just prior to use. Suitable inert carriers can include sugars such as lactose. Accordingly, in certain embodiment, the pharmaceutically acceptable vehicle, carrier, or excipient may be in a solid form, liquid form, or a suspension. In another non- limiting example, an oily solvent medium may also be used, and the oily solvent medium can be any pharmaceutically acceptable oil suitable to act as a solvent for the active ingredients. The oily solvent medium can be a vegetable oil or a nut oil, with one non- limiting example of the oily solvent medium being almond oil. In an exemplary embodiment of the present invention, the injectable pharmaceutical composition for use in treating or preventing Leishmaniasis is provided which comprises as active ingredients a dose of Itraconazole and a dose of Amiodarone, and in certain embodiments, the active ingredients can be in the form of a pharmaceutical composition that includes the active ingredient in a pharmaceutically acceptable vehicle, carrier, or excipient. In further embodiments, the pharmaceutical composition for use in treating Leishmaniasis may also include a second pharmaceutically acceptable vehicle, carrier, or excipient. In some embodiments, the presently disclosed subject matter provides that the dose of Itraconazole is first mixed with the second pharmaceutically acceptable carrier. The long-term method for treating or preventing Leishmania disease is carried out by a single injection of Itraconazole and Amiodarone in an amount effective to treat a subject in need thereof, and the method can use a single injection, or a second injection that is not required again for a long-term period such as 1.5, 3, 6, or 12 months after the first injection. The present compositions, methods, and uses are safer and longer lasting, more patient friendly, and provide a more effective way of treating or preventing Leishmaniasis than previously possible, and with fewer side effects. The present invention provides a pharmaceutical composition and form that improves upon the oral dosage form, and which is administered in the form of an injectable composition, such as in the form of a subcutaneous injection, an intramuscular injection, and / or implantable device. This injectable therapeutic composition allows for long-term treatment and prevention of Leishmaniasis in humans and animals, and in particular in mammals. The invention provides a method and composition for treatment or prevention that is long-lasting, but is carried out in such a manner that the overall length of therapy is significantly shorter than previous modes, and more patient friendly since it avoids the need for a continuous dosage regimen over a long period of time. As indicated herein, the present invention overcomes previous issues and concerns relating to the use of a combination of amiodarone and itraconazole because it has been difficult to develop a particularly suitable form of administration that could be used to provide long-term care in treating and preventing Leishmaniasis. As indicated above, these active ingredients have sometimes been associated with undesirable side effects such as cardiovascular problems or arrythmias. The present invention resulted from an attempt to improve the safety profile and long-term effectiveness of treatments that involved oral dosage forms. In particular, the ability to improve the safety profile by potentially administering significantly lower doses of each active ingredient was examined in terms of the relative bioavailability of an oral dosage form in comparison to a long-acting injectable dosage form. The present inventors thus discovered that this particular drug combination could be administered for long-term treatment or prevention of Leishmaniasis in lower doses and for a significantly shorter period of time when in a suitable injectable form, such as a subcutaneous injection, an intramuscular injection, and / or implantable device at proper levels of the active ingredients. The present injectable form further enhances safety and effectiveness because it overcomes issues of dosing compliance, drug resistance, reinfection and reluctance of companion animal owners to take responsibility for long-term daily dosing of the animal in need of treatment. As a result, the present long-term injectable system, method, and compositions also provides economic benefits because it lowers numbers of necessary treatments or administrations, and thus can be provided at a much lower costs than previous treatment compositions and methods of parasites such as those that cause Leishmaniasis. In one exemplary embodiment, an injectable long-term pharmaceutical composition is provided which has a lower dose of active ingredients compared to the oral dosage forms and is designed to deliver and maintain therapeutic blood levels of amiodarone and itraconazole in the blood of a patient or subject. In certain embodiments, a method of treating Leishmaniasis is provided wherein the dosage of the pharmaceutical composition of the invention is designed to result in sufficient therapeutic and biologically available amounts of Amiodarone and Itraconazole in the patient, and in one exemplary embodiment, a pharmaceutical composition is provided that contains a dosage of Amiodarone in an amount oi approximately from about 3.5 mg / kg to about 5.5 mg / kg of the subject or patient to be treated, and in another embodiment the desired range may be around 4.0 to around 5.0 mg / kg of the patient being treated. In the pharmaceutical composition of the invention, an amount of Itraconazole is also administered to the patient, and this may be in the range of approximately 2.0 mg / kg to about 8.0 mg / kg of the subject or the patient being treated, and in another embodiment this amount may be in the range of about 2.5 mg / kg to about 7.5 mg / kg of the subject or patient. It is possible to employ the active ingredients of the invention so that they are delivered in a single vial or pre-filled syringe containing both active ingredients of amiodarone and itraconazole. As set forth herein, the present inventors have found that the administration of a combination of Amiodarone and Itraconazole in injectable and / or implantable form can be utilized in a successful long-term treatment or prevention of Leishmaniasis in such a manner to greatly increase patient compliance. It is the inventors’ understanding that the normal mechanism of action for the amiodarone is that it disrupts mitochondrial Ca2+ homeostasis in the Leishmania parasite, and that the itraconazole acts as an antifungal agent which impairs ergosterol biosynthesis so as to affect certain enzymes and inhibit cell growth of parasites of the Leishmania species. In addition, Applicant’s injectable composition obtains the beneficial effects of a combination of itraconazole and amiodarone with these compounds in a bioavailable form and ensuring that these active ingredients will be in sufficient levels in the bloodstream or plasma of a subject undergoing the above treatment and / or prophylactic methods. In one embodiment of the present invention, the injectable form for long-term treatment or prophylaxis may be prepared by forming micrbht o-encapsulation matrices of the drug in biodegradable polymers such as polylactide- polyglycolide, poly(orthoesters) and poly(anhydrides). Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Other formulations allow localized release of the active ingredients when necessary. Injectable formulations of the invention may also be prepared by entrapping the drug in liposomes or microemulsions, which are compatible with body tissues. The injectable formulations can be sterilized, for example, by filtration through a bacterial- retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable media just prior to use. Suitable inert carriers can include sugars such as lactose. The formulation may also be sterilized via terminal sterilization processes including but not limited to steam sterilization, addition of ethylene oxide and / or radiation. Pharmaceutical compositions in accordance with the invention may be prepared in any suitable manner, and may be utilized in a single-vial or two-vial system. In one embodiment, the active ingredients are prepared in a two-vial system wherein one vial may contain the itraconazole and amiodarone in the ranges as specified herein. In one embodiment, these ingredients may be added to one of the vials together in amounts such as a range from about 1.0 to about 50 mg of Itraconazole, and from about 1.5 to about 75 mg of amiodarone. Such an amount will depend on the patient and will be adjusted based on patient size and condition to be administered within the levels of mg / kg as described herein. Other ingredients in the pharmaceutical composition of the invention that are included with the active ingredients in the first vial may be poly-d,l-lactide-co-glycolide in a range such as about 1-170 mg, mannitol USP in a range of from about 1-85 mg, carboxymethylcellulose sodium USP, such as in a range of about 1-30 mg, and polysorbate NF, such as in an amount of about 1-2 mg polysorbate. In this embodiment, a second vial is designed to be injected along with the first vial, and the second via may contain sterile water, such as in a range of 1-3mL, and this second vial may also be added to the first vial for injection. In additional embodiments of the present invention, the pharmaceutical composition as described herein may be in the form of a single pre-filled syringe containing both active ingredients such as in the amounts as indicated above. Still further, it is also possible to use two separate long-acting injectable formulations for Itraconazole and Amiodarone to be dosed at the same time. In yet another embodiment, the formulation may be prepared in a multi-use vial at various fixed concentrations that can be volumetrically adjusted to obtain the proper dose for patients of varying weights in order to achieve the maximally effective therapeutic or prophylactic doses as described in detail herein. The dosage form may also be in the form of a two vial system whereby one vial contains a lyophilized formulation containing active and inactive ingredients wherein the second vial contains water for reconstitution. Still another dosage formulation may be one that is injected via subcutaneous administration in which the formulation would be a pre-filled, multi-dose, adjustable syringe. As indicated above, the injectable formulations as set forth herein include suitable implantable forms that are biologically compatible and may be implanted into the subject or patient. In this form, there are many possible implants that may be used, include a drug eluting titanium implant which is designed for localized drug delivery. Accordingly, the injectable forms of the present invention can be manufactured and administered under a controlled process wherein the timing, location, and amount of the release is designed based on the needs of a particular subject or patient. In an exemplary embodiment of the method of the invention, a long-term treatment can be obtained by delivering the injection to the human or animal patient in such a manner so that another injection is not needed for a multi-month period. For example, it is possible to deliver the long-term injectable pharmaceutical composition of the invention once every one and a half months so that the treatment regimen is a total of three months, but any additional treatment would not need to be given again for another year. The present composition and method thus is able to administer a one-year treatment over the course of three months, and this is an improvement upon previous regimens of the active ingredients which must be taken regularly over the course of a year. In the present disclosure, the terms “treatment” or “treating” refer to the medical management of a subject with the intent to cure, ameliorate, stabilize, or prevent a disease, pathological condition, or disorder. This term includes active treatment, that is, treatment directed specifically toward the improvement of a disease, pathological condition, or disorder, and also includes causal treatment, that is, treatment directed toward removal of the cause of the associated disease, pathological condition, or disorder. In addition, this term incudes palliative treatment, that is, treatment designed for the relief of symptoms rather than the curing of the disease, pathological condition, or disorder; treatment directed to minimize or partially or completely inhibiting the development of the associated disease, pathological condition, or disorder; and supportive treatment, that is, treatment employed to supplement another specific therapy directed toward the improvement of the associated disease, pathological condition, or disorder. The term “administering” refers to any method of injecting a compound and / or injectable pharmaceutical composition thereof to a subject. Such methods are well known to those skilled in the art and include, but are not limited to, subcutaneous injection, intravenous administration, intra-arterial administration, intramuscular administration, and through implantation of a suitable and biologically compatible form to be implanted. Administration can be in accordance with the injection schedules for a subject or patient as described herein. In various aspects, the injectable preparation in accordance with the present invention can be administered to treat an existing disease or condition caused by the parasite of the genus Leishmania (e.g., Leishmaniasis),, or may be administered prophylactically; that is, administered for prevention of a disease or condition caused by a parasite of the species Leishmania. A listing of the Leishmania species that are treated by the present composition and method is included in Table 1 In some embodiments, the injectable pharmaceutical composition for use in treating or preventing Leishmaniasis will be administered to a subject in need thereof in an effective amount of the pharmaceutical composition. In this respect, the term “effective amount” refers to an amount that is sufficient to achieve the desired treatment result or to have an effect on the undesired condition being treated. For example, a “therapeutically effective amount” refers to an amount that is sufficient to achieve the desired therapeutic result or to have an effect on undesired symptoms, but that will reduce or eliminate adverse side effects. The specific therapeutically effective dose level for use in the treatment of any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration; the route of administration; the rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed and like factors well known in the medical arts. In further various aspects, a preparation can be administered in a “prophylactically effective amount”; that is, an amount effective for prevention of a disease or condition caused by parasites of the genus Leishmania.. Additionally, the terms “subject” or “subject in need thereof” or “patient” or “patient in need thereof” refer to a target of administration, which optionally displays symptoms related to a particular disease, pathological condition, disorder, or the like. The subject of the herein disclosed methods can be a vertebrate, such as a mammal, a fish, a bird, a reptile, or an amphibian. Thus, the subject of the herein disclosed methods can be a human, non-human primate, dog, horse, pig, rabbit, sheep, goat, cow, cat, guinea pig or rodent. The term does not denote a particular age or sex. Thus, adult and newborn subjects, as well as fetuses, whether male or female, are intended to be covered. A patient refers to a subject afflicted with a disease or disorder. The term “subject” includes human and veterinary subjects. In certain embodiments, a method of administration to achieve the long-term result of treatment or prevention using the injectable composition as described herein can comprise the delivery of the active ingredients in a single vial or pre-filled syringe containing both amiodarone and itraconazole actives delivered as a single injection which will then not need to be given again for another 12 months or longer. Such a treatment is effective against Leishmaniasis, long-lasting, and provide economic benefits because costs for the treatment for one year are significantly lower than other treatments that must be regularly given over the course of many months or a year. In accordance with the invention, a long-term injectable prophylactic formulation is also provided which contains an alternate dosage regimen designed to ensure protection against Leishmaniasis for an extended long-term period of from a few months to a year or longer. In one embodiment of the long-tern prophylactic therapy in accordance with the invention, Itraconazole and Amiodarone are administered in a long-term injectable form, but with generally lower amounts than the dosages above for long-term treatment methods. In one embodiment, the dosage may be around one-third of the dosage of the active ingredients when compared to the method of treatment as described hereinabove. This injectable composition is designed to deliver and maintain therapeutic blood levels of Itraconazole and amiodarone via a one-time or two-time dose that is protective for multiple months and up to one year or greater. In an exemplary embodiment, an injectable formulation is prepared containing approximately 0.5 to 5.5 mg / kg of Itraconazole per subject or patient and approximately 0.5 to 5.5 mg / kg of Amiodarone per subject or patient being administered the active ingredients. In another embodiment, the amount of Itraconazole administered may be in the range of from about 1.0 to about 5.0 mg / kg of a patient or subject, and the Amiodarone can be administered in an amount of from about 1.0 -5 mg / kg of the patient or subject. This dosage can be provided in any suitable injectable or implantable form such as a single vial or pre-filled syringe, but also can be administered separately at the same time. In an exemplary method of protecting a subject or patient against Leishmaniasis, the two active ingredients of Amiodarone and Itraconazole may be delivered in a single vial or pre-filled syringe or other implantable form designed to be administered once every six months, or two injections a year, and thus the protection from the present injectable composition will be for 12 months or longer. In another exemplary embodiment, the two active ingredients may be administered only once every 12 months for a total of one injection per year, and this method may be administered again when needed so as maintain protection against Leishmaniasis for a multi-year period. In one embodiment, injectable forms can be prepared by forming micro- encapsulation matrices of the active ingredients in biodegradable polymers such as polylactide-polyglycolides, poly(orthoesters), and / or poly(anhydrides). Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Injectable formulations may also be prepared by entrapping the active ingredients in liposomes or microemulsions, which are very compatible with body tissues. The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable media just prior to use. The formulation may also be sterilized via terminal sterilization processes including but not limited to Steam, Ethylene Oxide treatment, and Radiation. The formulations can also be prepared using suitable pharmaceutically acceptable vehicles, carriers or excipients, and in one suitable form, an inert carrier can be used which includes sugars such as lactose. Suitable injectable formulations of the present composition for use in treating or preventing Leishmaniasis may include aqueous and non-aqueous sterile injection solutions that can contain antioxidants, buffers, bacteriostats, bactericidal antibiotics and solutes that render the formulation isotonic with the bodily fluids of the intended recipient; and aqueous and non-aqueous sterile suspensions, which can include suspending agents and thickening agents. In another embodiment, drug formulations may be prepared that utilize a two-vial system, and in an exemplary embodiment, one vial may contain itraconazole in a range from 1-50 mg and amiodarone in a range from 1.5-75 mg. In exemplary embodiments, the active ingredients as used with a suitable and pharmaceutically acceptable vehicle, carrier or excipient. In some embodiments, other ingredients in the formulation in that vial may include poly-dl-lactide-co-glycolide, such as in amounts of 1-170 mg, mannitol USP, such as in amounts of 1-85 mg, carboxymethylcellulose sodium USP, such as in amounts of 1- 30 mg, and polysorbate 80 NF, such as in amounts of 1-2 mg . A second vial may contain 2 mL sterile water for injection to be added to the first vial. In another exemplary embodiment of the invention, a single pre-filled syringe containing both active ingredients is used in the method of treatment of and protection against Leishmaniasis. In yet another embodiment, two separate long-acting injectable formulations for Itraconazole and Amiodarone are dosed at the same time, or a multi-use vial at various fixed concentrations can be volumetrically adjusted to obtain the proper dose for patients of varying weights in order to achieve maximally effective therapeutic doses to provide the adequate blood levels of amiodarone and itraconazole in the patient. In another embodiment, the dosage form may include a two vial system whereby one vial contains the lyophilized formulation containing active and inactive ingredients and the second vial contains water for reconstitution. Another formulation for subcutaneous administration would be a pre-filled, multi-dose, adjustable syringe. Another may be a drug eluting titanium implant for localized drug delivery. As set forth herein, the present invention is advantageous because it provides a prophylactic dosage which allows the patient to substantially reduce or eliminate the risk of infection and disease caused by a parasite of the species Leishmania. This prophylactic method thus also substantially lowers or eliminates the risk for sever hepatic, kidney, and lymphatic system damage associated with chronic Leishmaniasis. In addition, the present injectable composition and method will also protect the patient against possible death that would be associated with acute and chronic L. Infantum infections. The present invention thus provides a prophylactic therapy that can be administered in even lower doses than either current oral or injectable treatment formulations, and the present invention allows for a period of treatment that has a significantly shorter period of time than current therapies, which even further enhances the drug combination safety profile. With regard to the treatment of the invention, this also allows for improving safety over the current oral dosage forms in that the present compositions will be administered at lower doses of each active ingredient because of the improved bioavailability of the present injectable form when compared with a form used in an oral dosage. The long-acting injectable pharmaceutical dosage form of the present invention when used for treating or preventing Leishmaniasis thus an improvement over current and previous forms of treatment or prevention because it can (1) overcome potential issues related to dosing compliance by the administration of either a bi-annual or annual injection to be done by the veterinarian; (2) avoid creating a drug resistance issue by ensuring long term therapy without interruption; (3) prevents against reinfection over a long period of time following the initial dose; (4) overcome the normal reluctance of companion animal owners to take responsibility for long-term daily dosing; (5) which results in significant economic benefits to the pet owner or patient because it involves a much lower use of the active ingredients that is effective for period of up to a year or longer. The long-term injectable pharmaceutical compositions for use in treating or preventing Leishmaniasis in accordance with the invention comprises as active ingredients a dose of Itraconazole and a dose of Amiodarone, and in certain embodiments, the active ingredients can be in the form of a pharmaceutical composition that includes the active ingredient in a pharmaceutically acceptable carrier. In further embodiments, the pharmaceutical composition for use in long-term treatment or prevention of Leishmaniasis may also include a second pharmaceutically acceptable carrier. In some embodiments, the presently disclosed subject matter provides that the dose of Itraconazole is first mixed with the second pharmaceutically acceptable carrier. In certain exemplary embodiments, the dosage of the active ingredients can be provided in a single vial, or they can also be administered simultaneously or separately to the patient. In general, the dosage should be provided at a level which results in suitable levels of the active ingredients in the blood stream of the patient. For example, the compositions of the invention should be sufficient to result in a plasma concentration in the patient of about 0.1 to 3.0 "g / ml of the active ingredients, or in another embodiment from about 0.3 to 2.0 "g / ml of the active ingredients. Still further, in another embodiment of the present invention, the long-term injectable pharmaceutical composition may have a dosage sufficient to result in a plasma concentration in the patient of from about 0.1 to about 3.0 "g / ml of Itraconazole, or from about 0.2 to about 3.0 "g / ml of Itraconazole. The dosage of Itraconazole may also be sufficient to provide a plasma concentration in the patient of at least 0.5 mcg / mL Itraconazole, or at least 1.0 mcg / mL Itraconazole. With regard to Amiodarone, in one embodiment, the levels of Amiodarone in the long-term injectable pharmaceutical composition of the invention are sufficient to result in a plasma concentration in the patient of from about 0.1 to about 3.0 "g / ml, or from about 1.5 to about 2.5 "g / ml in the patient. In accordance with the invention, a method for use in the long-term treatment of Leishmaniasis in a human or animal subject in need thereof is provided that comprises administering to said subject a long-term injectable composition comprising Amiodarone in the range of from about 3.5 mg / kg to about 5.5 mg / kg of the subject, and Itraconazole in the range of from about 2.0 mg / kg to about 8.0 mg / kg of the subject. These active ingredients may be administered along with a pharmaceutically acceptable vehicle, carrier, or excipient of such types that are well known in the art and used in many pharmaceutical compositions. In one embodiment of the inventive method, the Itraconazole and Amiodarone are administered together, or alternatively, the Itraconazole and Amiodarone may be are administered separately to the patient or subject. In another embodiment, the dosage of Amiodarone in the injectable composition may be in the range of from about 4.0 mg / kg to about 5.0 mg / kg of the subject, and the dose of Itraconazole may be in the range of from about 2.5 mg / kg to about 7.5 mg / kg of the subject. The method of treatment is designed so that only one or two injections are required to treat the patient for a long-term period of up to a year or longer. In the embodiments wherein two injections are employed, there is a long period following the first injection before a second injection needs to be administered. In certain embodiments, the second injection is administered one and a half months after the first injection, and then no additional injections will be needed for at least one year or longer. In this embodiment, the treatment period will thus be two injectable shots one and a half months apart, and this treatment will be effective for up to a year or longer. In cases wherein the treatment is successful and the Leishmaniasis has cleared, no additional treatment will be needed. In other embodiments of the method of the present invention, longer periods between the initial dose and the second dose may be provided. For example, it is possible to administer the first injection and then not administer the second injection for a period of three months or six months, or any period in between these two time frames. In both cases, the treatment regimen will be only two injections that will provide effective treatment for one year or longer. In an another embodiment, a one-time dosage of the injectable composition as described above is provided and then not administered for at least 12 months. In such a method, there is only a single injection that will provide effective treatment of Leishmaniasis for one year or longer. As indicated above, the injectable form for containing the active ingredients of the invention may be any suitable injectable form such as a form of a subcutaneous injection or a muscular injection, or as indicated above, the term injectable includes the use of an implantable device which may be implanted into the patient Implantable drug delivery systems (sometimes referred to as IDDSs) provide a variety of ways of implanting an active drug into a patient, and such systems and devices may be bioengineered and then surgically placed inside the patient's tissues where needed to obtain the maximum effect of the active ingredients inside the patient. Such imputable devices can be used advantageously because they can avoid problems such as first-pass metabolism, and they can also reduce the systemic toxicity of the drug by having the active ingredients released only in the vicinity of target tissues when needed. In an exemplary embodiment of the present method, the dose of Amiodarone and Itraconazole is sufficient to result in an effective amount of these active ingredients in the patient. In one embodiment of the present method, the dose of Amiodarone and Itraconazole is sufficient to result in a plasma concentration in the patient of from about 0.1 to about 3.0 "g / ml of the active ingredients. In other embodiments, the dose is sufficient to result in a plasma concentration in the patient of from about 0.3 to about 2.0 "g / ml of the active ingredients. In other embodiments of the method, the injectable pharmaceutical composition used in this method may have a dosage sufficient to result in a plasma concentration of from about 0.1 to about 3.0 "g / ml of Itraconazole in the patient, or from about 0.2 to about 3.0 "g / ml of Itraconazole in the patient. In certain embodiments, the dosage of Itraconazole may also be sufficient to provide a plasma concentration in the patient of at least 0.5 mcg / mL Itraconazole, or at minimum 1.0 mcg / mL of Itraconazole. With regard to Amiodarone, in one embodiment, the levels of Amiodarone in the long-term injectable pharmaceutical composition used in thus method will be sufficient to result in a plasma concentration of from about 0.1 to about 3.0 "g / ml Amiodarone in the patient, or from about 1.5 to about 2.5 "g / ml Amiodarone in the patient. In certain embodiments, the total dose of Itraconazole in the injectable forms of the invention may be from about 1 mg to about 50 mg; and the dose of Amiodarone in such forms may be from about 1.5 mg to about 75 mg. In certain treatment regimens, the patient may be provided with food at or around the time of the injections. In accordance with the invention, a method for use in the long-term prevention of Leishmaniasis in a human or animal subject in need thereof is also provided that comprises administering to said subject a long-term injectable composition comprising Amiodarone in the range of from about 0.5 mg / kg to about 5.5 mg / kg of the subject, and Itraconazole in the range of from about 0.5 mg / kg to about 5.5 mg / kg of the subject. In particular, any dosage within this range is contemplated for use in the long-term treatment of Leishmaniasis, as well as any smaller range within the larger range. For example dosages of either Itraconazole or Amiodarone may be at every 0.5 mg / kg interval within the total range, namely the lower limit may be about 0.5 mg / kg, about 1.0 mg / kg, about 1.5 mg / kg, and so forth all the way throughout the range to the upper limit. These active ingredients may be administered along with a pharmaceutically acceptable vehicle, carrier, or excipient of such types that are well known in the art and used in many pharmaceutical compositions. In one embodiment of the inventive method, the Itraconazole and Amiodarone are administered together, or alternatively, the Itraconazole and Amiodarone may be are administered separately to the patient or subject. In another embodiment, the dosage of Itraconazole may be in the range of from about 1.0 mg / kg to about 5.0 mg / kg of the subject, and the dosage of Amiodarone is in the range of from about 1.0 mg / kg to about 5.0 mg / kg of the subject. The method of prophylaxis is designed so that only one or two injections are required to treat the patient for a long-term period of up to a year or longer. In the embodiments wherein two injections are employed, there is a long period following the first injection before a second injection needs to be administered. In certain embodiments, the second injection is administered three months after the first injection, and then no additional injections will be needed to provide protection against Leishmaniasis for at least one year or longer. In this embodiment, the full extent of the prophylaxis regimen will thus be two injectable shots three months apart, and this treatment will be effective for up to a year or longer. Additional injections in accordance with the invention may take place as needed following the initial 12 months. In other embodiments of the method of prophylaxis of the present invention, longer periods between the initial dose and the second dose may be provided. For example, it is possible to administer the first injection and then not administer the second injection for a period of six months. In both cases, the regimen will be only two injections that will provide effective protection against Leishmaniasis for one year or longer. In an another embodiment, a one-time dosage of the injectable composition as described above is provided and then not administered for at least 12 months. In such a method, there is only a single injection that will provide effective prevention of Leishmaniasis for one year or longer. As indicated above, the injectable form for containing the active ingredients of the invention for use in the prophylactic method may be any suitable injectable form such as a form of a subcutaneous injection or a muscular injection, or as indicated above, the term injectable includes the use of an implantable device which may be implanted into the patient Implantable drug delivery systems (or IDDSs) as described above may also be utilized. In an exemplary embodiment of the present prophylactic method, the dose of Amiodarone and Itraconazole is sufficient to result in an effective amount of these active ingredients in the patient. In one embodiment of the present method, the dose of Amiodarone and Itraconazole is sufficient to result in a plasma concentration in the patient of from about 0.1 to about 3.0 "g / ml of the active ingredients. In other embodiments, the dose is sufficient to result in a plasma concentration in the patient of from about 0.3 to about 2.0 "g / ml of the active ingredients. In other embodiments of the prophylactic method, the injectable pharmaceutical composition used in this method may have a dosage sufficient to result in a plasma concentration of from about 0.1 to about 3.0 "g / ml of Itraconazole in the patient, or from about 0.2 to about 3.0 "g / ml of Itraconazole in the patient. In certain embodiments, the dosage of Itraconazole may also be sufficient to provide a plasma concentration in the patient of at least 0.5 mcg / mL Itraconazole, or at minimum 1.0 mcg / mL of Itraconazole. With regard to Amiodarone, in one embodiment, the levels of Amiodarone in the long-term injectable pharmaceutical composition used in thus method will be sufficient to result in a plasma concentration of from about 0.1 to about 3.0 "g / ml Amiodarone in the patient, or from about 1.5 to about 2.5 "g / ml Amiodarone in the patient. In certain embodiments, the total dose of Itraconazole in the injectable forms used for prophylaxis against leishmaniasis may be from about 1 mg to about 50 mg; and the dose of Amiodarone in such forms may be from about 1.5 mg to about 75 mg. As indicated above, the prophylactic injectable composition used in the present method may be in any suitable form that can be safely injected into a patient, such as a subcutaneous injection, a muscular injection, or an implantable device. In another embodiment of the invention, a long-term injectable pharmaceutical composition for use in long-term treatment of Leishmaniasis is provided which comprises a dose of Amiodarone in an amount of from about 3.5 mg / kg to about 5.5 mg / kg of the subject, a dose of Itraconazole in an amount of from about 2.0 mg / kg to about 8.0 mg / kg of the subject; and a pharmaceutically acceptable carrier. In an alternate embodiment, the long-term injectable pharmaceutical composition for use in long-term treatment of Leishmaniasis may include a dose of Amiodarone in the range of about 4.0 mg / kg to about 5.0 mg / kg, and a dose of Itraconazole in the range of about 2.5 mg / kg to about 7.5 mg / kg. The injectable composition may be in the form of a single vial or container containing both of the active ingredients, and in still other injectable forms, the Itraconazole and Amiodarone may be provided to the patient in separate vials or containers. The long-term injectable pharmaceutical composition for treatment of Leishmaniasis may be designed so that dose is sufficient to result in a plasma concentration in the patient of from about 0.1 to 3.0 "g / ml of the active ingredients, or from about 0.3 to about 2.0 "g / ml of the active ingredients. A method for long-term treatment of Leishmaniasis in a human or animal subject in need thereof thus comprises administering to the subject an effective amount of this long-term pharmaceutical composition. In another embodiment, a long-term injectable pharmaceutical composition for use in long-term prevention of Leishmaniasis is provided which comprises a dose of Amiodarone in an amount of from about 0.5 mg / kg to about 5.5 mg / kg of the subject, a dose of Itraconazole in an amount of from about 0.5 mg / kg to about 5.5 mg / kg of the subject; and a pharmaceutically acceptable carrier. In an alternate embodiment, the long- term injectable pharmaceutical composition for use in long-term treatment of Leishmaniasis may include a dose of Amiodarone in the range of about 1.0 mg / kg to about 5.0 mg / kg, and a dose of Itraconazole in the range of about 1.0 mg / kg to about 5.0 mg / kg. In general, the long-term injectable pharmaceutical composition may be in the form of a single vial or a pre-filled syringe. The injectable composition may be in the form of a single vial or container containing both of the active ingredients, and in still other injectable forms, the Itraconazole and Amiodarone may be provided to the patient in separate vials or containers. The long-term injectable pharmaceutical composition for prevention of Leishmaniasis may be designed so that dose is sufficient to result in a plasma concentration in the patient of from about 0.1 to 3.0 "g / ml of the active ingredients, or from about 0.3 to about 2.0 "g / ml of the active ingredients. In summary, a method for preventing or treating Leishmaniasis in a human or animal subject in need thereof is [provided that comprises administering to the subject an effective amount of this long-term pharmaceutical composition. As indicated above, the methods of the invention may be used to achieve long-term treatment or prevention of Leishmaniasis in human or animal subjects in need thereof. In certain embodiments, the subject may be a mammal, and the mammal may be selected from the group consisting of a human, a dog, a cat, a monkey, or other mammal that might be domesticated or retained in preserves or in zoos, and the subject may be a pet. ` Still further, a use of itraconazole and amiodarone for the manufacture of a medicament for the long-term treatment of Leishmaniasis in a human or animal subject in need thereof is provided, and this medicament may be a pharmaceutical composition having a dose of itraconazole in the range of about 2.5 mg / kg to about 7.5 mg / kg of a subject, and a dose of amiodarone in the range of about 4.0 mg / kg to about 5.0 mg / kg of the subject. ` In another embodiment, a use of itraconazole and amiodarone for the manufacture of a medicament for the long-term prevention of Leishmaniasis in a human or animal subject in need thereof is provided, and this medicament may be a pharmaceutical composition having a dose of itraconazole in the range of about 1.0 mg / kg to about 5.0 mg / kg of a subject, and a dose of amiodarone in the range of about 1.0 mg / kg to about 5.0 mg / kg of the subject. The presently-disclosed subject matter is further illustrated by the following specific but non-limiting examples. Some of the following examples are prophetic, notwithstanding the numerical values, results and / or data referred to and contained in the examples as set forth below. EXAMPLES The examples below refer to methods of preparation as well as long-term treatment and / or prevention of Leishmaniasis using an injectable combination of Itraconazole and Amiodarone in accordance with the present invention. EXAMPLE 1 In one embodiment of preparing the Itraconazole for use in the injectable compositions and methods in accordance with the present invention, the Itraconazole can be nanometrically milled using conventional wet milling equipment well known in the art. In one suitable process, itraconazole (1%, w / v) can be suspended in a desired concentration of an aqueous stabilizer solution, and the prepared suspension can be stirred for 30 minutes or more for complete wetting of the drug by the stabilizer solution. The suspension (e.g., 150 mL) may then be wet milled or wet grinded using a conventional wet milling or grinding device such as a media mill, for example, such as those manufactured by Netzsch of Exton, Pennsylvania. Using this equipment, the mill may be operated at a suitable speed, e.g., 2500 rpm in a continuous mode for a time suitable to reduce particle size to a range of 1 and 400 nm, e.g., 75 minutes. The temperature of the sample can be maintained at below 25ºC during the process, and as needed, two cooling bath recirculators may be used, including one attached to the milling device and the other attached to suspension recirculation chambers. After the milling process, the nano- and microcrystalline suspensions of itraconazole may be spray dried onto a suitable substrate, such as a sugar molecule (e.g., lactose or mannitol) using a conventional spray drying apparatus such as a B-290 spray drier manufactured by Buchi Labortechnik AG of Flawil, Switzerland. In the spray drying process, the drier is set at a suitable temperature, e.g.75ºC for the outlet and 110 ºC for the inlet. The spray drying uses a suitable excipient, e.g., lactose or mannitol, to protect against nanocrystal aggregation, and spray-dried powders resulting from this process contain itraconazole at a reduced particle size, e.g., 1-400 nm. EXAMPLE 2 In another exemplary embodiment, the method of long-term treatment using the injectable composition of the invention as described herein can also have a pre-treatment period wherein the subject is provided with a conventional treatment with a tablet comprising a combination of Amiodarone and Itraconazole. Such tablets are known in the art, such as disclosed in Madigan et al., J. Am. Vet. Med. Assoc.255(3): 317-329 (2019), or can be prepared in conventional ways to prepare such a pharmaceutical tablet. In an exemplary embodiment, the tablet will have a higher dosage of the active ingredients than as described herein for the present invention. For example, the tablet when used in canine treatment may have a dosage of about 50 mg of Itraconazole and about 75 mg of Amiodarone, and when used in feline treatment, the tablet may have a dosage of about 25 mg Itraconazole and about 37.5 mg of Amiodarone. These tablets may contain Itraconazole that is prepared using a hot melt extrusion (HME) process that would be known to those skilled in the art. Such a pretreatment step may be for a period of up to about one month. Following the completion of the pre-treatment dosage regiment, the long-term injectable composition of the invention may then be administered to the subject or patient as described herein. In one suitable example, following the 30-day or month-long treatment with the tablets, either one or two long-acting injections of the pharmaceutical composition of the invention described herein can be administered to the patient so as to provide treatment for a full year or longer. In an exemplary treatment method of the invention, an injectable composition containing the two active ingredients of Amiodarone and Itraconazole is prepared to be delivered to a patient or subject in need of treatment for Leishmaniasis. In a suitable example, the treatment method will be in the form of an injectable pharmaceutical composition containing Amiodarone in the range of from about 3.5 mg / kg to about 5.5 mg / kg of the subject, and Itraconazole in the range of from about 2.0 mg / kg to about 8.0 mg / kg of the subject. These active ingredients may be administered along with a pharmaceutically acceptable vehicle, carrier, or excipient of such types that are well known in the art and used in many pharmaceutical compositions. In one embodiment of the inventive method, the Itraconazole and Amiodarone are administered together, or alternatively, the Itraconazole and Amiodarone may be are administered separately to the patient or subject. In another embodiment, the dosage of Amiodarone in the injectable composition may be in the range of from about 4.0 mg / kg to about 5.0 mg / kg of the subject, and the dose of Itraconazole may be in the range of from about 2.5 mg / kg to about 7.5 mg / kg of the subject.. In the exemplary embodiment, these active ingredients are delivered in a single vial, pre-filled syringe, or other implantable form designed to be administered in one or two injections a year, and the duration of treatment can be from three months to a year. In either of these treatment methods, one or two injections can provide treatment of an infected patient for a year, and thus the treatment is provided by the injection of the present composition for 12 months or longer on the basis of just one or two injections a year. EXAMPLE 3 In an exemplary treatment method of the invention, an injectable composition containing the two active ingredients of Amiodarone and Itraconazole is prepared to be delivered to a patient or subject in need of such treatment. In one embodiment, these active ingredients are delivered in a single vial, pre-filled syringe, or other implantable form designed to be administered once every six months, or two injections a year, and thus the present injectable composition will be useful for treating Leishmania over a long-term period such as 12 months. In another exemplary embodiment, the two active ingredients may be administered only once every 12 months for a total of one injection per year. The injectable treatment forms of the invention can be prepared by forming micro- encapsulation matrices of the active ingredients in biodegradable polymers such as polylactide-polyglycolides, poly(orthoesters), and / or poly(anhydrides). Alternately, the active ingredients are prepared by entrapping the active ingredients in liposomes or microemulsions, which are very compatible with body tissues. The injectable formulations can be sterilized by filtration through a bacterial-retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable media just prior to use. The formulation may also be sterilized via terminal sterilization processes such as steam, ethylene oxide, or radiation. The formulations also include suitable pharmaceutically acceptable vehicles, carriers or excipients, and in one suitable example, an inert carrier can be used which includes sugars such as lactose. Suitable injectable formulations of the present composition for use in treating Leishmaniasis may include aqueous and non-aqueous sterile injection solutions that can contain antioxidants, buffers, bacteriostats, bactericidal antibiotics and solutes that render the formulation isotonic with the bodily fluids of the intended recipient; and aqueous and non-aqueous sterile suspensions, which can include suspending agents and thickening agents. In another example, drug formulations are prepared in a two-vial system wherein one vial contains itraconazole in a range from 1-50 mg and amiodarone in a range from 1.5-75 mg. The precise amount to be included will depend on the size and condition of the patient being treated. As indicated herein, in a suitable example of a composition for long- term treatment of Leishmaniasis, the injectable formulation will contain Amiodarone in an amount of from about 4.0 mg / kg to about 5.0 mg / kg of the subject, and the amount of Itraconazole in the injectable pharmaceutical composition will be in the range of from about 2.5 mg / kg to about 7.5 mg / kg of the subject. The active ingredients are used with a pharmaceutically acceptable vehicle, carrier or excipient. In this example, the formulation includes poly-dl-lactide-co-glycolide in an amounts of 1-170 mg, mannitol USP in an amount of 1-85 mg, carboxymethylcellulose sodium USP in an amount of 1-30 mg, and polysorbate 80 NF in an amount of 1-2 mg . In this two-vial system, a second vial is also prepared that contains 2 mL sterile water which is added to the first vial and then injected into the patient. In the long-term method of the invention, a single dosage may provide treatment for up to 12 months of longer, or a second injection may be administered six months after the first, thus providing a system wherein only two injections in a single year are needed to treat Leishmaniosis. EXAMPLE 4 In other examples in accordance with the invention, a single pre-filled syringe containing both active ingredients is used in the method of treatment of and protection against Leishmaniasis. In yet another embodiment, two separate long-acting injectable formulations for Itraconazole and Amiodarone are dosed at the same time, or a multi-use vial at various fixed concentrations can be volumetrically adjusted to obtain the proper dose for patients of varying weights in order to achieve maximally effective therapeutic doses to provide the adequate blood levels of amiodarone and itraconazole in the patient. This dosage form may include a two vial system whereby one vial contains the lyophilized formulation containing active and inactive ingredients and the second vial contains water for reconstitution. Another formulation for subcutaneous administration would be a pre- filled, multi-dose, adjustable syringe. Another may be a drug eluting titanium implant for localized drug delivery. The long-acting injectable pharmaceutical dosage form of the present invention when used for treating Leishmaniasis improves upon current forms because it can (1) overcome potential issues related to dosing compliance by the administration of either a bi-annual or annual injection to be done by the veterinarian; (2) avoid creating a drug resistance issue by ensuring long term therapy without interruption; (3) prevent against reinfection over a long period of time following the initial dose; (4) overcome the normal reluctance of companion animal owners to take responsibility for long-term daily dosing; and (5) this results in significant economic benefits to the pet owner or patient because it involves a much lower use of the active ingredients that is effective for treatment against Leishmaniasis for a period of up to a year or longer. EXAMPLE 5 In an exemplary prophylactic method of the invention, an injectable composition containing the two active ingredients of Amiodarone and Itraconazole is prepared to be delivered to a patient or subject in need of such protection against Leishmania infection. In one embodiment, these active ingredients are delivered in a single vial, pre-filled syringe, or other implantable form designed to be administered once every six months, or two injections a year, and thus the protection is provided by the injection of the present composition for 12 months or longer on the basis of just two injections a year. In another exemplary embodiment, the two active ingredients may be administered once and then not administered again for at least 12 months to provide a prophylactic system which only requires one injection per year. The injectable prophylactic forms of the invention can be prepared by forming micro-encapsulation matrices of the active ingredients in biodegradable polymers such as polylactide-polyglycolides, poly(orthoesters), and / or poly(anhydrides). Alternately, the active ingredients are prepared by entrapping the active ingredients in liposomes or microemulsions, which are very compatible with body tissues. The injectable formulations can be sterilized by filtration through a bacterial-retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable media just prior to use. The formulation may also be sterilized via terminal sterilization processes such as steam, ethylene oxide, or radiation. The formulations also include suitable pharmaceutically acceptable vehicles, carriers or excipients, and in one suitable example, an inert carrier can be used which includes sugars such as lactose. Suitable injectable formulations of the present composition for use in preventing Leishmaniasis may include aqueous and non-aqueous sterile injection solutions that can contain antioxidants, buffers, bacteriostats, bactericidal antibiotics and solutes that render the formulation isotonic with the bodily fluids of the intended recipient; and aqueous and non-aqueous sterile suspensions, which can include suspending agents and thickening agents. In one particular example, the prophylactic drug formulations are prepared in a two- vial system wherein one vial contains itraconazole in a range from 1-50 mg and amiodarone in a range from 1.5-75 mg. The precise amount to be included will depend on the size and condition of the patient receiving the prophylactic treat as described herein. As indicated herein, in a suitable example of a composition for long-term protection against Leishmaniasis, the injectable formulation will be prepared such that an individual dosage will contain Amiodarone in an amount of from about 0.5 mg / kg to about 5.5 mg / kg of the subject, and will contain Itraconazole in an amount in the range of from about 0.5 mg / kg to about 5.5 mg / kg of the subject. The active ingredients are used with a suitable and pharmaceutically acceptable vehicle, carrier or excipient. In this example, the formulation includes poly-dl-lactide-co- glycolide in an amounts of 1-170 mg, mannitol USP in an amount of 1-85 mg, carboxymethylcellulose sodium USP in an amount of 1-30 mg, and polysorbate 80 NF in an amount of 1-2 mg . In this two-vial system, a second vial is also prepared that contains 2 mL sterile water which is added to the first vial and then injected into the patient. As indicated above, in the long-term method of the present invention, this initial dosage may be sufficient to provide protection against Leishmaniasis for up to 12 months of longer, or a second injection may be administered six months after the first, thus providing a system wherein only two injections in a single year are needed to prevent Leishmaniosis in a human or animal subject or patient. The long-acting injectable prophylactic dosage form of the present invention when used for preventing Leishmaniasis improves upon current forms because it can (1) overcome potential issues related to dosing compliance by the administration of either a bi-annual or annual injection to be done by the veterinarian; (2) avoid creating a drug resistance issue by ensuring long term therapy without interruption; (3) prevent against reinfection over a long period of time following the initial dose; (4) overcome the normal reluctance of companion animal owners to take responsibility for long-term daily dosing; and (5) this results in significant economic benefits to the pet owner or patient because it involves a much lower use of the active ingredients that is effective for protection against Leishmaniasis for a period of up to a year or longer. EXAMPLE 7 In an exemplary test of the method and use of the compositions of the disclosure, an injectable composition containing the two active ingredients of Amiodarone and Itraconazole is prepared and tested with regard to the stability necessary for long-term treatment and protections against diseases caused by parasites of the Leishmania species. In this testing, formulations were made using a combination of Itraconazole and Amiodarone in HCl microspheres. The dosages of these formulations were as follows: Scope Itraconazole Amiodarone HCl Ratio Itra / Amio On the basis of above dosages, several formulation of microspheres were produced maintaining the ratio between Itraconazole and Amiodarone HCl, as described below. Composition of microspheres The complete compositions of the formulations are shown in the table below, expressed as mg per 100 mg of microspheres. In the testing, samples T1S and T3S are formulated for prevention and treatment of Leishmaniasis.

[0002] Composition of reconstitution liquid Compositions of formulations in reconstitution liquid is shown in the Table below: Methyl-parahydroxybenzoate 1.89 (mg) Packaging Each formulation is packaged in a 30 ml vial containing 3.6 g of lipid microspheres and a 20 ml vial containing at least 17 ml of reconstitution liquid. By adding exactly 16 ml of reconstitution liquid in the microspheres vial, the formulation's final concentration will be: Formulation Number Formulation Ingredients Dissolution Testing and Conditions for the dissolution test Equipment In-vitro release studies were conducted using Apparatus 4 (Sotax CE7 smart, Sotax AG, Switzerland, Sotax CP 7-35 piston pump, Sotax AG, Switzerland and Sotax C615 autosampler, Sotax AG, Switzerland), with flow-through cells (22.6-mm diameter) packed with glass beads (1 mm) in a closed system mode at 37°C, in conformity with the Ph. Eur. current edition (2.9.3 “Dissolution test for solid dosage forms”). Reagents Ortho-phosphoric acid, reagent grade; Sodium phosphate dibasic, reagent grade’ Sodium Lauryl Sulphate (SLS), technical grade Purified water Operating Conditions -Apparatus: Type IV, Flow-through cells -Temperature: 37.0 ± 0.5 °C -Flow rate: 16 ml / min -Sampling times: Every 6 hours up to 144 hours -Volume of medium: 1000 ml -Dissolution medium: pH 7.4: HNa2PO40.01M, at pH 7.4 with H3PO485%, 0.25% SLS -Sample: 100 mg of microspheres per cell -Number of samples: 3 samples per batch -Size of sample: 1.0 ml Conducting the Test Laminar flow with a bed of glass beads was used for all the tests. The degassed dissolution medium pH 7.4 phosphate buffer, enriched with 0.25% SLS (1000 ml), maintained at 37.0 ± 0.5 °C, was pumped at a flow rate of 16 mL / min. The closed-loop system was achieved by recycling the dissolution medium. A ruby bead (5 mm diameter) was placed at the base of the 22.6 mm sample cell and 4 g of 1 mm glass beads were added to fill the conical bottom part of the sample cell. The sample of microspheres was placed on the top of these glass beads, and then covered with a final layer of glass beads. At each time point, 1 ml was taken and directly analysed by HPLC. The solution volume taken at each sampling was restored using an equivalent volume of corresponding dissolution medium. Sink conditions were maintained throughout the experiment. The analysis was conducted using an HPLC method. A schematic of this method and apparatus is shown in Fig.1. Test Results Obtained Table 1 and Table 2 below lists the mean percentage values of dissolved Amiodarone HCl and Itraconazole respectively, they are the means of the values obtained at To, 1 month and 3 months. Regarding 3 replicates of each formulation at each time point and at a pH of 7.4, 0.25% SLS. The results obtained are expressed as a percentage of the total theoretical quantity of active substance contained in 100 mg of microspheres in 1000 ml of dissolution medium. The cumulative percentages of the active ingredient dissolved at each time point were used to create the dissolution profiles.

[0003] )shh 2 3 5 5h4 2 4t2 n 7 om3h6 d 6 nahtn h o 06m1,o T hf45onae h8 M(4 SLSh 5 1 0 4 h 7 5 26 7420 3% 4 52.0,h4.637H ptha03 desaelher42lCHe h n 8o1r a doih 0 1 2 8 7 29.2 1.9h65 5 2m 1 6.4 6 7.4.6 0 8 01.6.7.9 2 8 0A 9fos 5 9 8 1 0 5 9 1e hu68.l92.4.h 3 5 35.85.5 0 7 85.0.3.8 1 99 1aveg na%n%na%n%ate D ae D e D ae Dn m S m S m S S R m RelR Cl lR Cl l lCl lcrSHCHCHC C H C e 1 e SHS e SHS1 e S1HS S e 3 e 3HepT n 1 orT e 3 n T n 3 T e n T n ooro orT n T n ororT n on ara ara a ard a aa deoid d d oioioioid d oioid oiMm m m m m:A m m A A A A A A m A 1leba T h 7 25.8 7 0.7h5 47.4 9 7 70.26 .0.57 3 54.4 0 9.8 6 1 01 3 9 3 2 ) h 4 62.8 4 6.4 h84.4 2 3 02s 6 38. .7.8.7 2 14.3 8 6 1 0 8 1 3 9 3 no 3 2 8 9 c artIfh 7 27.6 9 4 h 9 2 8 4 o 1 54.1.2 4 18.43.1 2 8 47.3.8 3 98.8 6 se ul9 a h 0 1 3 h 0 9 8 3 v 64.25.9.4.88.1 5 3 2 7 07.2.8 3 71.8 7 e g atne crn%n%n e ae D a n e D a% %e D ae D p SmS S S nma 1lR R m me elelelelRS o 1 S o S3 oz S3 o 1 1elelReSoS S o Sle T za T z T a T z TzToz3 T za 3 TozM n a a a : o n n c o o n n an n a c o o o o n o 2arca a c c rtaarc c a a c rta eltIrtI I rtI tIrtI I rtIba T Additional Results Obtained In addition to the information provided above, Figure 2 and Figure 3 are provided herein which graphically provide the dissolution profiles of Amiodarone HCl and Itraconazole contained in the T1S sterilized formulation (Figure 2) and Dissolution profiles of Amiodarone HCl and Itraconazole contained in the T3S sterilized formulation (Figure 3). Testing Conclusion According to the data collected, Itraconazole has a slower kinetic of release than Amiodarone HCl. This can be explained with the less solubility of Itraconazole, whose kinetic of dissolution is quite comparable to the one of Moxidectin in Afilaria SR. The dissolution profiles of T1S (formulated for treatment of the Leishmania) appear to be the best among the various formulations. In light of these tests and the data showing multiple months of stability of the compositions of the disclosure.as shown in the figures (see the low RSD %), this confirms that the formulations are stable long term and are capable of carrying out the methods and uses as set forth above.

[0004] Table 1: List of Leishmania species by subgenus Subgenus Leishmania Ross, 1903 sensu Saf'janova, 1982 · Leishmania aethiopica Bray, Ashford & Bray, 1973 · Leishmania amazonensis Lainson & Shaw, 1972 (includes garnhami Scorza et al., 1979) · Leishmania arabica Peters, Elbihari & Evans, 1986 · Leishmania aristidesi Lainson & Shaw, 1979 · Leishmania donovani (Laveran & Mesnil, 1903) · Leishmania forattinii Yoshida, Cuba, Pacheco, Cupolillo, Tavares, Machado, Homen & Grimaldi, 1993 · Leishmania gerbilli Wang, Qu & Guan, 1964 · Leishmania infantum Nicolle, 1908 (subspecies chagasi Cunha & Chagas, 1937) · Leishmania killicki Rioux, Lamotte & Pratlong, 1986 · Leishmania major Yakimoff & Schokhor, 1914 · Leishmania mexicana Biagi, 1953 · Leishmania pifanoi Medina & Romero, 1959 · Leishmania tropica (Wright, 1903) · Leishmania turanica Strelkova, Shurkhal, Kellina, Eliseev, Evans, Peters, Chapman, Le Blancq & van Eys, 1990 · Leishmania venezeulensis Bonfante-Garrido, 1980 · Leishmania waltoni Shaw, Pratlong & Dedet 2015 Subgenus Mundinia Shaw,Camargo and Teixeira 2016 · Leishmania enriettiiMuniz & Medina, 1948 · Leishmania macropodum Barratt, Kaufer, Peters, Craig, Lawrence, Roberts, Lee, McAuliffe, Stark, Ellis, 2017 · Leishmania martiniquensis Desbois, Pratlong, Quist and Dedet,2014

[0026] · Leishmania orientalis Jariyapan, Daroontum, Jaiwong, Sor-Suwan, Siriyasatien, Somboon, Bates, Bates, 2018 Subgenus Sauroleishmania Ranque, 1973 sensu Saf'janova, 1982 · Leishmania adleri Heisch, 1958 · Leishmania agamae David, 1929 · Leishmania ceramodactyli Adler & Theodor, 1929 · Leishmania gulikae Ovezmukhammedov & Saf'janova, 1987 · Leishmania gymnodactyli † Khodukin & Sofiev, 1940 · Leishmania helioscopi † Chodukin & Sofiev, 1940 · Leishmania hemidactyli Mackie, Gupta & Swaminath, 1923 · Leishmania hoogstraali McMillan, 1965 · Leishmania nicollei Chodukin & Sofieff, 1940 · Leishmania platycephala Telford, 2009 · Leishmania phrynocephali Chodukin & Sofieff, 1940 · Leishmania senegalensis Ranque, 1973 ·Leishmania sofieffi ↑ Markov, Lukina & Markova, 1964· Leishmania tarentolae Wenyon, 1921 ·Leishmania zmeevi ↑ Andruchko & Markov 1955· Leishmania zuckermani Paperna, Boulard, Hering-Hagenbeck & Landau, 2001↑ Species described as Sauroleishmania. Their development is not like other membersof the subgenus and so their taxonomic position is doubtful. Subgenus Viannia Lainson & Shaw 1987 · Leishmania braziliensis Vianna, 1911 · Leishmania guyanensis Floch, 1954 · Leishmania lainsoni Silveira, Shaw, Braga & Ishikawa, 1987 · Leishmania lindenbergi Silveira, Ishikawa, De Souza & Lainson, 2002 · Leishmania naiffi Lainson & Shaw, 1989 · Leishmania panamensis Lainson & Shaw, 1972 · Leishmania peruviana Velez, 1913 · Leishmania shawi Lainson, Braga & de Souza, 1989 · Leishmania utingensis Braga, Lainson, Ishikawa & Shaw 2003 .

Claims

CLAIMS What is claimed is:

1. A long-term injectable pharmaceutical composition for treating Leishmaniasis comprising: (a) a dose of Amiodarone in the range of from about 3.5 mg / kg to about 5.5 mg / kg of the subject, and (b) a dose of Itraconazole in the range of from about 2.0 mg / kg to about 8.0 mg / kg of the subject.

2. The long-term injectable pharmaceutical composition of claim 1 wherein the Itraconazole and Amiodarone are administered in a pharmaceutically acceptable carrier.

3. The long-term injectable pharmaceutical composition of claims 1 or 2 wherein the Itraconazole and Amiodarone are administered together..

4. The long-term injectable pharmaceutical composition of claims 1 or 2 wherein the Itraconazole and Amiodarone are administered separately.

5. The long-term injectable pharmaceutical composition of any of the preceding claims wherein the dose of Amiodarone is in the range of from about 4.0 mg / kg to about 5.0 mg / kg of the subject, and wherein the dose of Itraconazole is in the range of from about 2.5 mg / kg to about 7.5 mg / kg of the subject.

6. The long-term injectable pharmaceutical composition of any of the preceding claims wherein the Itraconazole and Amiodarone are administered once and not administered again for at least 1.5 months.

7. The long-term injectable pharmaceutical composition of any of the preceding claims wherein the Itraconazole and Amiodarone are administered once and not administered again for at least 6 months.

8. The long-term injectable pharmaceutical composition of any of the preceding claims wherein the Itraconazole and Amiodarone are administered once and is not administered again for at least 12 months.

9. The long-term injectable pharmaceutical of any of the preceding claims wherein the composition is injected in the form of a subcutaneous injection, a muscular injection, or an implantable device.

10. The long-term injectable pharmaceutical composition of any of the preceding claims, wherein the dose is sufficient to result in a plasma concentration in the patient of from about 0.1 to about 3.0 "g / ml of the active ingredients.

11. The long-term injectable pharmaceutical composition of any of the preceding claims, wherein the dose is sufficient to result in a plasma concentration in the patient of from about 0.3 to about 2.0 "g / ml of the active ingredients.

12. The long-term injectable pharmaceutical composition of any of claims 1-10, wherein the dose is sufficient to result in a plasma concentration in the patient of from about 0.1 to about 3.0 "g / ml of Itraconazole.

13. The long-term injectable pharmaceutical composition of any of claims 1-10, wherein the dose is sufficient to result in a plasma concentration in the patient of from about 0.2 to about 3.0 "g / ml of Itraconazole.

14. The long-term injectable pharmaceutical composition of any of claims 1-10, wherein the dose is sufficient to result in a plasma concentration in the patient of at least 0.5 mcg / mL Itraconazole.

15. The long-term injectable pharmaceutical composition of any of claims 1-10, wherein the dose is sufficient to result in a plasma concentration in the patient of at least 1.0 mcg / mL Itraconazole.

16. The long-term injectable pharmaceutical composition of any of claims 1-10, wherein the dose is sufficient to result in a plasma concentration in the patient of from about 0.1 to about 3.0 "g / ml of Amiodarone.

17. The long-term injectable pharmaceutical composition of any of claims 1-10, wherein the dose is sufficient to result in a plasma concentration in the patient of from about 1.5 to about 2.5 "g / ml of Amiodarone.

18. A long-term injectable pharmaceutical composition for preventing Leishmaniasis in a patient comprising: (a) a dose of Itraconazole wherein the dose of Itraconazole is in the range of from about 0.5 mg / kg to about 5.5 mg / kg of the subject, and (b) a dose of Amiodarone wherein the dose of Amiodarone is in the range of from about 0.5 mg / kg to about 5.5 mg / kg of the subject.

19. The long-term injectable pharmaceutical composition of claim 18 wherein the Itraconazole and Amiodarone are administered in a pharmaceutically acceptable carrier.

20. The long-term injectable pharmaceutical composition of claims 18 or 19 wherein the Itraconazole and Amiodarone are administered together..

21. The long-term injectable pharmaceutical composition of claims 18 or 19 wherein the Itraconazole and Amiodarone are administered separately.

22. The long-term injectable pharmaceutical composition of any of claims 18-21 wherein the dose of Itraconazole is in the range of from about 1.0 mg / kg to about 5.0 mg / kg of the subject, and wherein the dose of Amiodarone is in the range of from about 1.0 mg / kg to about 5.0 mg / kg of the subject.

23. The long-term injectable pharmaceutical composition of any of claims 18-22 wherein the Itraconazole and Amiodarone are administered once and not administered again for at least 3 months.

24. The long-term injectable pharmaceutical composition of any of claims 18-23 wherein the Itraconazole and Amiodarone are administered once and not administered again for at least 6 months.

25. The long-term injectable pharmaceutical composition of any of claims 18-24, wherein the Itraconazole and Amiodarone are administered once and is not administered again for at least 12 months.

26. The long-term injectable pharmaceutical of any of claims 18-25, wherein the composition is injected in the form of a subcutaneous injection, a muscular injection, or an implantable device.

27. The long-term injectable pharmaceutical composition of any of claims 18-26, wherein the dose is sufficient to result in a plasma concentration in the patient of from about 0.1 to about 3.0 "g / ml of the active ingredients.

28. The long-term injectable pharmaceutical composition of any of claims 18-27, wherein the dose is sufficient to result in a plasma concentration in the patient of from about 0.3 to about 2.0 "g / ml of the active ingredients.

29. A method for use in long-term treatment of Leishmaniasis in a human or animal subject in need thereof, comprising administering a long-term injectable composition comprising: (a) a dose of Amiodarone in the range of from about 3.5 mg / kg to about 5.5 mg / kg of the subject, and (b) a dose of Itraconazole in the range of from about 2.0 mg / kg to about 8.0 mg / kg of the subject.

30. The method of claim 29 wherein the Itraconazole and Amiodarone are administered in a pharmaceutically acceptable carrier.

31. The method of claims 29 or 30 wherein the Itraconazole and Amiodarone are administered together..

32. The method of claims 29 or 30 wherein the Itraconazole and Amiodarone are administered separately.

33. The method of any of claims 29-32 wherein the dose of Amiodarone is in the range of from about 4.0 mg / kg to about 5.0 mg / kg of the subject, and wherein the dose of Itraconazole is in the range of from about 2.5 mg / kg to about 7.5 mg / kg of the subject.

34. The method of any of claims 29-33 wherein the Itraconazole and Amiodarone are administered once and not administered again for at least 1.5 months.

35. The method of any of claims 29-34 wherein the Itraconazole and Amiodarone are administered once and not administered again for at least 6 months.

36. The method of any of claims 29-35 wherein the Itraconazole and Amiodarone are administered once and not administered again for at least 12 months.

37. The method of any of claims 29-36 wherein the composition is injected in the form of a subcutaneous injection, a muscular injection, or an implantable device.

38. The method of any of claims 29-37, wherein the dose is sufficient to result in a plasma concentration in the patient of from about 0.1 to about 3.0 "g / ml of the active ingredients.

39. The method of any of claims 29-38, wherein the dose is sufficient to result in a plasma concentration in the patient of from about 0.3 to about 2.0 "g / ml of the active ingredients.

40. The method of any of claims 29-39 wherein the dose of Itraconazole of from about 1 mg to about 50 mg; and the dose of Amiodarone of from about 1.5 mg to about 75 mg.

41. A method for use in long-term prevention of Leishmaniasis in a human or animal subject in need thereof, comprising administering a long-term injectable composition comprising: (a) a dose of Itraconazole wherein the dose of Itraconazole is in the range of from about 0.5 mg / kg to about 5.5 mg / kg of the subject, and (b) a dose of Amiodarone wherein the dose of Amiodarone is in the range of from about 0.5 mg / kg to about 5.5 mg / kg of the subject.

42. The method of claim 41 wherein the Itraconazole and Amiodarone are administered in a pharmaceutically acceptable carrier.

43. The method of claims 41 or 42 wherein the Itraconazole and Amiodarone are administered together..

44. The method of claims 41 or 42 wherein the Itraconazole and Amiodarone are administered separately.

45. The method of any of claims 41-44 wherein the dose of Itraconazole is in the range of from about 1.0 mg / kg to about 5.0 mg / kg of the subject, and wherein the dose of Amiodarone is in the range of from about 1.0 mg / kg to about 5.0 mg / kg of the subject.

46. The method of any of claims 41-45 wherein the Itraconazole and Amiodarone are administered once and not administered again for at least 3 months.

47. The method of any of claims 41-46 wherein the Itraconazole and Amiodarone are administered once and not administered again for at least 6 months.

48. The method of any of claims 41-47 wherein the Itraconazole and Amiodarone are administered once and not administered again for at least 12 months.

49. The method of any of claims 41-48 wherein the composition is injected in the form of a subcutaneous injection, a muscular injection, or an implantable device.

50. The method of any of claims 41-49, wherein the dose is sufficient to result in a plasma concentration in the patient of from about 0.1 to about 3.0 "g / ml of the active ingredients.

51. The method of any of claims 41-50, wherein the dose is sufficient to result in a plasma concentration in the patient of from about 0.3 to about 2.0 "g / ml of the active ingredients.

52. The method of any of claims 41-51 wherein the dose of Itraconazole is from about 1 mg to about 50 mg; and the dose of Amiodarone is from about 1.5 mg to about 75 mg.

53. A long-term injectable pharmaceutical composition for use in long-term treatment of Leishmaniasis, comprising: (a) a dose of Amiodarone in an amount of from about 3.5 mg / kg to about 5.5 mg / kg of the subject, (b) a dose of Itraconazole in an amount of from about 2.0 mg / kg to about 8.0 mg / kg of the subject; and (c) a pharmaceutically acceptable carrier.

54. The long-term injectable pharmaceutical composition of claim 53 wherein the dose of Amiodarone is in the range of about 4.0 mg / kg to about 5.0 mg / kg.

55. The long-term injectable pharmaceutical composition of claim 53 or 54 wherein the dose of Itraconazole is in the range of about 2.5 mg / kg to about 7.5 mg / kg.

56. The long-term injectable pharmaceutical composition of any of claims 53-55 wherein the dose is sufficient to result in a plasma concentration in the patient of from about 0.1 to 3.0 "g / ml of the active ingredients.

57. The long-term injectable pharmaceutical composition of any of claims 53-56, wherein the dose is sufficient to result in a plasma concentration in the patient of from about 0.3 to about 2.0 "g / ml of the active ingredients.

58. A method of treating Leishmaniasis in a human or animal subject in need thereof, comprising: administering to the subject an effective amount of the long-term pharmaceutical composition of any of claims 53-57.

59. A long-term injectable pharmaceutical composition for use in long-term prevention of Leishmaniasis, comprising: (a) a dose of Itraconazole wherein the dose of Itraconazole is in the range of from about 0.5 mg / kg to about 5.5 mg / kg of the subject, (b) a dose of Amiodarone wherein the dose of Amiodarone is in the range of from about 0,5 mg / kg to about 5.5 mg / kg of the subject; and (c) a pharmaceutically acceptable carrier.

60. The long-term injectable pharmaceutical composition of claim 59 wherein the dose of Itraconazole is in the range of about 1.0 mg / kg to about 5.0 mg / kg.

61. The long-term injectable pharmaceutical composition of claim 59 or 60 wherein the dose of Amiodarone is in the range of about 1.0 mg / kg to about 5.0 mg / kg.

62. The long-term injectable pharmaceutical composition of any of claims 59-61 wherein the dose is sufficient to result in a plasma concentration in the patient of from about 0.1 to 3.0 "g / ml of the active ingredients.

63. The long-term injectable pharmaceutical composition of any of claims 58-62, wherein the dose is sufficient to result in a plasma concentration in the patient of from about 0.3 to about 2.0 "g / ml of the active ingredients.

64. The long-term injectable pharmaceutical composition of any of claims 53-63, wherein the composition is in the form of a single vial or a pre-filled syringe.

65. A method of preventing Leishmaniasis in a human or animal subject in need thereof, comprising: administering to the subject an effective amount of the pharmaceutical composition of any of claims 64-68.

66. The method of claim 65, wherein the subject is a mammal.

67. The method of claims 65 or 66, wherein the subject is selected from the group consisting of a human, a dog, a cat, and a monkey.

68. Use of itraconazole and amiodarone for the manufacture of a medicament for the long-term treatment of Leishmaniasis in a human or animal subject in need thereof.

69. The use of claim 68 wherein the dose of itraconazole is in the range of about 2.5 mg / kg to about 7.5 mg / kg of a subject, and the dose of amiodarone is in the range of about 4.0 mg / kg to about 5.0 mg / kg of the subject.

70. Use of itraconazole and amiodarone for the manufacture of a medicament for the long-term prevention of Leishmaniasis in a human or animal subject in need thereof.

71. The use of claim 70 wherein the dose of itraconazole is in the range of about 1.0 mg / kg to about 5.0 mg / kg of a subject, and the dose of amiodarone is in the range of about 1.0 mg / kg to about 5.0 mg / kg of the subject.

72. The use of claim 70 wherein the itraconazole and amiodarone are used in a diluent formulation comprising a two-vial system wherein one vial contains lyophilized micelles encapsulating the combination of itraconazole and amiodarone as active ingredients and wherein the second vial contains a diluent which is combined with the lyophilized micelles to create the final formulation.

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