FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
PROVISIONAL SPECIFICATION
[See section 10 and rule 13]
1. TITLE: RE-ESTABLISHMENT OF BLOOD FLOW IN BLOCKED HUMAN ARTERIES BY TRANSFERRING NANO-ENCAPSULATED DRUG THROUGH MEDICAL DEVICES, DESIGNED FOR THE SAME AND RELEASING THE NANO-ENCAPSULATED DRUG IN HUMAN ARTERY WITH BODY pH
2. APPLICANTS:
1. Envision Scientific Private Limited ,
8, Narayan Darshan Apartment, Opp. Rupam Cinema, Salabatpura, Surat (Gujarat), INDIA , PIN- 395002 NATIONALITY : Indian
2. Concept Medical Research Private Limited
D-512A, International Trade Center, Near Majuragate, Ring Road, Surat {Gujarat), INDIA, PIN-395003 NATIONALITY : Indian
The following specification describes the invention


RE-ESTABLISHMENT OF BLOOD FLOW IN BLOCKED HUMAN ARTERIES
BY TRANSFERRING NANO-ENCAPSULATED DRUG THROUGH MEDICAL
DEVICES, DESIGNED FOR THE SAME AND RELEASING THE NANO-
ENCAPSULATED DRUG IN HUMAN ARTERY WITH BODY pH
FIELD OF THE INVENTION
[0001] The invention generally relates to a method and system for administrating drug to a target site through a medical device. More specifically, the invention relates to a Drug Releasing Medical Device coated with different sized nano-particles of one or more drugs for efficient delivery of the one or more drugs across the various layers of body vessel.
BACKGROUND
[0002] Several medical devices are used for performing interventional surgical procedures to widen the lumen of a blocked body vessel. For example, stents are used for re-establishment of a proper blood flow in blocked arteries in a coronary angioplasty procedure, such as, Percutaneous Transluminal Coronary Angioplasty (PTCA). However, there are several disadvantages associated with the existing interventional surgical procedures and medical devices used therefore. For example, in certain instances, the widening of the lumen of the artery may be followed by one or more of restenosis, acute thrombosis, sub-acute thrombosis, and late thrombosis.
[0003] To reduce the incidences of restenosis that occur following angioplasty procedures, Drug Releasing Medical Devices (DRMDs), like, Drug Releasing Stents (DRS), are often used. However, it is observed that the polymers used for forming a coating around the DRMDs and to facilitate release of drug from the DRMD may trigger inflammation at the site of blockage. The inflammation may further lead to thrombus formation as a result of body's physiological immune response. The thrombus may further aggravate resulting in the blocking of the artery.

[0004] Also, the particle sizes of the drugs as well as the polymers that are coated around the DRMDs are larger than the sizes of the tissue pores. Therefore, a substantial amount of drug remains unabsorbed. The unabsorbed drug gets washed away in blood stream and produce unwanted side effects. For example, currently used DRSs are loaded with more than 100 micro-grams of drug of which, only 12 to 25 nano-gram of the drug can penetrate the tissue. Rest of the drug either is washed away in the blood stream from the inner surface of DRS or is released over time. Further, loading more than 100 micro¬grams of drug requires higher amounts of polymer to be loaded on to the DRSs. This may lead to acute thrombosis, sub-acute thrombosis, late thrombosis. In addition, the inner side of the DRSs is coated with drug, which may affect endothialisation of tissues. This may lead to an improper healing or a delayed healing respectively.
[0005] Further, the currently used DRMDs are associated with edge restenosis and focal restenosis. One of the major reasons for edge restenosis is that during the deployment of stents, the edges of stents can cause injury to a lesion. Another reason for edge restenosis is that some portion of the lesion is adequately supplied with drug by the DRSs while some portion of the lesion (region not covered by the DRS) is very poorly or not at all supplied with the drug by the DRSs. The portion of the lesion that is adequately supplied with the drug may possibly remain less prone to restenosis as compared with the portion of the lesion that is poorly supplied or not at all supplied with the drug. In the currently used DRSs, generally, only 10% to 20% of a portion of a lesion is covered by a DRS. Thus, the currently used DRS do not guarantee the delivery of one or more drugs to the entire portion of the lesion.
[0006] Additionally, most of the drugs that are administered to a patient using the current DRMDs are hydrophobic in nature and have less affinity for body tissues. As a result, a high amount of the drug needs to be loaded in the DRSs for achieving the desired therapeutic effect.

[0007] There is therefore a need in the art for improved DRMDs and methods for preparing the same, which reduce instances of restenosis, acute thrombosis, sub-acute thrombosis, late thrombosis, and delayed healing. In addition, there is a need in the art for DRMDs that provide for a size-dependent penetration of drug across the various layers of body vessel such that, the drug is supplied to the entire region of the target site. Further, there is a need for DRMDs that provide for enhanced bioavailability and biocompatibility of the drug. Also, there is a need in the art for DRMDs that can efficiently address the various therapeutic windows of the cell cycle of tissues of the target site.
DETAILED DESCRIPTION
[0008] Before describing in detail embodiments that are in accordance with the invention, it should be observed that the embodiments reside primarily in combinations of components of a drug releasing medical device and method steps of preparing the same. Accordingly, the components and the method steps have been described to include only those specific details that are pertinent to understanding the embodiments of the invention so as not to obscure the disclosure with details that will be readily apparent to those of ordinary skill in the art having the benefit of the description herein.
[0009] In this document, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. An element preceded by "comprises ...a" does not. without more constraints, preclude the existence of additional identical elements in the process, method, article, or apparatus that comprises the element.
[0010] Further, before describing in detail embodiments that are in accordance with the invention, it should be observed that all the scientific and technical terms used in for

describing the invention have same meanings as would be understood by a person skilled in the art.
[0011] Generally speaking, pursuant to various embodiments, the invention discloses a Drug Releasing Medical Device (DRMDs) with different sized nano-encapsulated particles of one or more drugs coated around an abiuminal surface of the DRMD which provide for efficient drug delivery across one or more layers of a body vessel.
[0012] Pursuant to the various embodiments of the invention, the DRMD includes one or more of, but not limited to, a stent, a balloon, and a stent mounted on a balloon. The DRMD further includes one or more surfaces that come in a close proximity of a target site for local delivery of one or more drugs at the target site. The one or more surfaces come in the close proximity of the target site upon insertion of the DRMD into the body and upon positioning the DRMD at the target site. The close proximity may include a physical contact of the target site with the one or more surfaces. Alternatively, the close proximity may include any distance between the target site and the one or more surfaces that is less than 1 mm. The one or more portions of the one or more surfaces are coated with the nano-encapsulated particles of two or more average diameters.
[0013] In an embodiment of the invention, the two or more average diameters of the nano-encapsulated particles may correspond to two or more pore sizes of one or more layers of a blood vessel. When the one or more surfaces come in close proximity of the target site, the nano-encapsulated particles are released from the DRMD and penetrate the one or more layers of the blood vessel. The nano-encapsulated particles with two or more average diameter penetrate two or more layers of the one or more layers of the blood vessel based upon different average diameters of pores of the one or more layers of the blood vessel. Thus, a size-dependent penetration of a drug across the one or more layers of the blood vessel may be achieved by using the nano-encapsulated particles of the two or more average diameters.

[0014] The nano-encapsulated particles of the invention may be obtained by
encapsulating nano-particles of one or more drugs with one or more of. but not limited to,
one or more excipients obtained from blood, one or more phospholipids. The one or more
phospholipids may include one or more phospholipids obtained from one or more of,
natural sources and synthetic process. For example, the one or more phospholipids may
include phosphatidylcholines, phosphatidylglycerol, phosphatidy (inositol,
phosphatidyJserine, phosphatidic acid, cardiolipin, and phosphatidy]ethanoJamine. The one or more lipoids may include, for example, but not limited to, phospholipon 80H, phospholipon 90H, Lipoids S75, Lipoids E80, Intralipid 20, Lipoid EPC, Lipoids E75, lipids obtained from egg, and lipids obtained from soya.
[0015] The nano-encapsulated particles thus obtained show better affinity for the target site and hence provide for a better absorption of the one or more drugs by the target site. The DRMD may include a stent mounted on a balloon, such that one or more portions of the stent and one or more portions of the balloon are coated with the nano-encapsulated particles of one or more drugs. The one or more portions of the balloon coated with the nano-encapsulated particles provides for an immediate release of the one or more drugs upon coming in close proximity of the target site. Further, the one or more portions of the stent coated with the nano-encapsulated particles provides a sustained release of the one or more drugs upon coming in close proximity of the target site.
[0016] In accordance with the various embodiments of the invention, the DRMD is any implantable or non-impiantable medical device that can be inserted or implanted either into a body or on the body of an animal including human beings. Examples of DRMD may include, but not limited to, a stent, a catheter, a catheter balloon, a stent mounted on a catheter balloon, a spinal implant, a balloon catheter, a percutaneous implant, a transdermal drug delivery device, a dental implant any surgical implant, and any other medical device that can be inserted into a human body for delivery of one or more drugs at a particular site in an human body. In an instance, when the DRMD is a stent, it may include one or more of, but not limited to, a cardiovascular stent, a peripheral stent, an

intracranial stent, renal stent, and carotid stent. The stent may be made up of one or more of, but not limited to, a metal, an alloy, a biodegradable polymer, and a non-degradable polymer.
[0017] In an exemplary embodiment of the invention, the stent is made up of one or more of, but not limited to, SS316LVM, L605 Cobalt Chromium alloy, Dimond Like Coating (DLC) coated stent, Hydroxy Appetite Phosphate (HAP) coated stent, carbon coated stent, platinum activated stent, and nickel-titanium alloy. Additionally, the one or more surfaces of the stent may be coated with one or more of, but not limited to, a biodegradable polymer, bio-absorbable polymer, and a non-degradable polymer.
[0018] In accordance with the various embodiments of the invention, the DRMD is a Drug Releasing Stent (DRS). The one or more portions of the DRS are coated with nano-encapsulated particles of one or more drugs. The nano-encapsulated particles are of two or more different average diameters. For example, the DRS may be coated with nano-encapsulated particles with a first average diameter, nano-encapsulated particles with a second average diameter, and nano-encapsulated particles with a third average diameter. The first average diameter may be approximately 40% to 80% smaller than the third average diameter. More preferably, the first average diameter is approximately 60% to 70% smaller than the third diameter. For example, the first average diameter is less than 400 nanometer and the third diameter is greater than 800 nanometer. The second average diameter ranges between 400 nanometer to 800 nanometer. It will be appreciated by a person skilled in the art that any combination of different sizes of the nano-encapsulated particles may be used to achieve a size-dependant penetration of drug into the pores across the different layers of tissues at the target site, without deviating from the scope of the invention.
[0019] Generally, the DRSs are used to deliver drug to the target site in the blood vessel. The blood vessel is made up of three layers namely, intima, media and adventitia. The average size of pores of the tissues of adventitia is generally less than 400 nanometer.

The average size of pores of the tissues of media is generally between 400 nanometer to 800 nanometer whereas, the average size of pores of the tissues of intima is generally greater than 800 nanometer. The nano-encapsulated particles with the first average diameter, the second average diameter, and the third average diameter thus penetrate and get located in adventitia, media, and intima respectively. Therefore, a size-dependent penetration of a drug may be achieved across the different layers of the blood vessel. The nano-encapsulated particles with the first average diameter, the second average diameter, and the third average diameter are used to deliver drug to adventitia, media, and intima respectively. The drug will penetrate adventitia and media through vaso vasorum.
[0020] The nano-encapsulated particles with the first average diameter penetrate into adventitia. The nano-encapsulated particles with the first average diameter remain in the adventitia for a prolonged time and adventitia thus acts as a reservoir of the one or more drugs. The one or more drugs are released from the reservoir over a prolonged period thereby providing a sustained therapeutic effect of the one or more drugs. Further, the nano-encapsulated particles with the second average diameter will penetrate into media and provide for a prolonged release thereby resulting in a prolonged therapeutic effect of the one or more drugs. The prolonged therapeutic effect provided by the nano-encapsulated particles with the second average diameter will be of lesser duration as compared to the prolonged therapeutic effect provided by the nano-encapsulated drug particles with the first average diameter. This provides for a prolonged in-tissue release of one or more of the one or more drugs over a period. Similarly, the nano-encapsulated particles with the third average diameter will be absorbed in the intima. The nano-encapsulated particles that are absorbed at intima may provide for an immediate therapeutic effect of the one or more drugs.
[0021] The nano-encapsulated particles with the first average diameter, the second average diameter, and the third average diameter may include the nano-particles of same or different drugs. For example, the nano-encapsulated particles with the first average diameter, the second average diameter, and the third diameter may include a same drug. The drug may be one of, but not limited to, an anti-inflammatory agent, an ami-

thrombotic agent, an antiproliferative agent, estrogens, healing promoters, an antibiotic, a protease inhibitor, one or more antibodies, an anti-mitotic agent, an immunosuppressive agent, a cytostatic agent, a cytotoxic agent, a calcium channel blocker, and anti-platelet aggregating agent. For example, the drug may include, one or more of, but not limited to, paclitaxel, sirolumus, dexamethasone, genistine, Isoflovon, heparin, beta-estradiol, rapamycin, Everolimus, Zotralimus, BiolimusA9, Mayolimus, Novalimus, Pemecrolimus, Tacrolimus, Cyclosporine, and Statins. Further, the drug may include one or more of analogue and substitute of the drug.
[0022] In another embodiment of the invention, the nano-encapsulated particles of the first average diameter, the second average diameter, and the third average diameter, may each include one or more different drugs to address one or more therapeutic needs of a eel] cycle of the tissue. In order to address one or more therapeutic needs of a cell cycle of the tissue, the nano-encapsulated particles with the first average diameter are released earlier as compared to the nano-encapsulated particles with the second average diameter and the third average diameter. Therefore, the nano-encapsulated particles with the first average diameter deliver one or more drugs that are required to address the initial phases of a cell cycle of the tissue. For example, the nano-encapsulated particles with the first average diameter address the first phase of the cell cycle of the tissue like, thrombus formation and inflammation. To address the first phase of cell cycle, the nano-encapsulated particles of the first average diameter may include one or more of, but not limited to, anti-thrombotic agent and anti-inflammatory agent. The nano-encapsulated particles with the first average diameter provide for delivery of the one or more of, but not limited to, anti-thrombotic agent and anti-inflammatory agent to the target site, upon coming in the close proximity of the target site. Thus, the nano-encapsulated particles with the first average diameter address the first phase of the cell cycle of the tissue.
[0023] Similarly, the nano-encapsulated particles with the second average diameter address a second phase of the cell cycle of the tissue. As the second phase of the cell cycle of the tissue includes the process of cell proliferation, the nano-encapsulated particles with the second average diameter may include one or more anti proliferative

agents. The nano-encapsulated particles with the second average diameter provide for delivery of the one or more anti proliferative agents to the target site, upon coming in the close proximity of the target site. Thus, the nano-encapsulated particles with the second average diameter are used to address the second phase of the cell cycle of the tissue. Further, the nano-encapsulated particles with the third average diameter may be used to address a third phase of the cell cycle of the tissue. Accordingly, the nano-encapsulated particles with the third average diameter may include one or more of, but not limited to, estrogen receptor and healing promoter. The nano-encapsulated particles with the third average diameter provide for delivery of the one or more of, estrogen receptor and healing promoters to the target site, upon coming in the close proximity of the target site. The nano-encapsulated particles of the third average diameter are used to address the third phase of the cell cycle of the tissue and promote healing of the lesion. Thus, the nano-encapsulated particles with the two or more different average diameters may be used to deliver different drugs in order to address the different phases of the cell cycle of the tissue.
[0024] It will be appreciated by a person skilled in the art that any combination of one or more drugs may be included in the nano-encapsulated particles with the first average diameter, the second average diameter, and the third average diameter, to address one or more particular therapeutic needs, without deviating from the scope of the invention.
[0025] In accordance with the various embodiments of the invention, the nano-encapsulated particles may include nano-particles of a drug encapsulated with a suitable encapsulating medium. The suitable encapsulating medium includes, for example, one or more of, but not limited to, one or more biodegradable polymers, one or more bioabsorbable polymer, one or more non biodegradable polymers, one or more excipients obtained from blood, one or more excipients related to blood, one or more naturally occurring phospholipids, one or more artificially manufactured phospholipids, and one or more lipoids. For example, the encapsulating medium includes, one or more of, but not limited to, one or more excipients obtained from blood, one or more naturally occurring phospholipids, and one or more lipoids. Alternatively, the encapsulating medium may

include one or more naturally occurring substances that have affinity for the tissue. When one or more of, one or more excipients obtained from blood, one or more naturally occurring phospholipids, and one or more lipoids are used for encapsulation of the nano-particles of a drug, the nano-encapsulated particles thus formed show high affinity for the tissues at target sites. Thus, the drug may penetrate the tissue with an ease, thereby reducing amount of the drug to be loaded onto the DRS which in turn reduces the amount of polymer to be loaded onto the DRS resulting in minimized toxicity otherwise associated with the higher doses of the drug.
[0026] In an embodiment of the invention, one or more excipients obtained from blood and one or more phospholipids may be used for encapsulation of the nano-particles of a drug. The one or more excipients obtained from blood impart the nano-encapsulated particles with an affinity towards the tissues of the target site. Whereas, the one or more phospholipids owing to presence of one hydrophilic head and two hydrophobic tails stabilize the nano-encapsulated particles and excipients. In addition, the one or more phospholipids have a characteristic to promote healing. Thus, the one or more phospholipids provide for a timely healing of the lesion.
[0027] Further, when the one or more excipients obtained from blood are used for encapsulating the nano-particles of one or more drugs, the nano-encapsulated particles thus obtained possess a pH value that is closely in range of pH value of the tissues of the target site. Therefore, when the nano-encapsulated particles come in contact with the tissues of the target site, the nano-encapsulated particles are easily released. Thus, a pH dependent release of the one or more drugs from the DRS may be used to release a drug of the one or more drugs at the target site efficiently. Thus, the one or more excipients from blood and the one or more phospholipids provide for better penetration of the drug into the tissue and thereby provide enhanced biocompatibility and bioavailability. The enhanced biocompatibility and bioavailability in turn, results in a small loading dose thereby minimizing complications such as toxicity, inflammation, and thrombogenicity.

[0028] The encapsulation of the nano-particles of the drug according to various embodiments of the invention, may be achieved by known methods. For example, one or more of, but not limited to, aerosol coating, spray coating, dip coating, and pan coating may be used for encapsulation of the nano-particles of the drug. Further, in addition to the encapsulation medium, one or more suitable excipients may also be used for encapsulation of nano-particles of the drug.
[0029] In accordance with another embodiment of the invention, the DRMD includes a DRS and a catheter balloon. The DRS is either mounted or crimped on the catheter balloon. The one or more portions of the catheter balloon not covered by the DRS, are coated with the nano-encapsulated particles. Further, the one or more portions of the catheter not covered by the DRS include one or more of, a distal end of the catheter balloon extending beyond a corresponding edge of the DRS and a proximal end of the catheter balloon that extends beyond a corresponding edge of the DRS. One or more portions of both the DRS and the catheter balloon are coated with the nano-encapsulated particles, such that the nano-encapsulated particles coated on the one or more portions of the catheter balloon provide an immediate release of the one or more drugs and the nano-encapsulated particles coated on the one or more portions of the DRS provide for a sustained release of the one or more drugs. Further, the nano-encapsulated particles coated on the distal end and the proximal end of the catheter balloon provide for delivery of the one or more drugs to the tissues at the corresponding edges of the DRS. Thus, the instances of edge-restenosis may be efficiently reduced. In addition, the coating of the nano-encapsulated particles on the one or more portions of the catheter balloon ensures delivery of the one or more drugs to the entire affected portion of the tissue and thus minimizes the instances of focal restenosis.
[0030] According to another embodiment of the invention, the one or more drugs coated on the catheter balloon and the DRS are same. Alternatively, different drugs may be coated on the catheter balloon and the DRS to address different therapeutic needs. Further, the nano-encapsulated particles are coated only on abluminal surface of the DRS,

whereas the luminal surface of the DRS is substantially free of the nano-encapsulated particles. Coating the nano-encapsulated particles on the abluminal surface of the DRS provides for enhanced endothealization. Generally, if a therapeutic agent is also present on the luminal surface of the DRS, some amount of the therapeutic agent gets dissolved in the blood and may affect process of endothealization because of property of anti¬proliferative or immune-suppressive properties of the therapeutic agent. The effect of the therapeutic agent on the endothealization is optimized by coating the nano-encapsulated particles only on the abluminal surface of the DRS. However, it will be appreciated by a person skilled in the art that> both luminal and abluminal surface of the DRS may be coated with the nano-encapsulated particles, without deviating from the scope of the invention.
[0031] Pursuant to the various embodiments of the invention, a method for preparing a Drug Releasing Medical Device (DRMD) is disclosed. The method includes, preparing nano-particles of one or more drugs, encapsulating nano-particles of the one or more drugs with one or more encapsulating mediums to obtain nano-encapsulated particles of the one or more drugs, and subsequently coating the nano-encapsulated particles of the one or more drugs on abluminal surface of the DRMD.
[0032] According to various embodiments of the invention, the nano-particles of the one or more drugs may be obtained by known method, for example, but not limited to, milling, pulverizing, and spray drying. The process of preparing the nano-particles of the one or more drugs further includes reducing the size of one or more drug substances using an appropriate method so as to get the nano-particles of the one or more drugs with two or more different average diameters. For example, the nano-particles of the one or more drugs obtained in the above step may have one of, but not limited to, a first average diameter, a second average diameter and a third average diameter.
[0033] Subsequently, the nano-particles of the one or more drugs are coated with the one or more encapsulating mediums. The one or more encapsulating mediums may include,

for example., but not limited to, one or more biodegradable polymers, one or more non biodegradable polymers, one or more bioabsorbable polymer, one or more excipients obtained from blood, one or more naturally occurring phospholipids, one or more artificially manufactured phospholipids, and one or more lipoids. For example, the encapsulating medium includes, one or more of, but not limited to one or more excipients obtained from blood, one or more naturally occurring phospholipids, and one or more lipoids. Alternatively, the encapsulating medium may include one or more naturally occurring substances that have affinity for the tissue.
[0034] The nano-encapsulated particles thus obtained are then coated on the abluminal surface of the DRMD by using known methods. The DRMD may include one or more of, a stent, a balloon, and a stent mounted or crimped on a balloon. For example, the nano-encapsulated particles of the one or more drugs may be coated on the abluminal surface of the stent mounted or crimped on the balloon such that, one or more portions of the balloon that is not covered by the stent also gets coated with the nano-encapsulated particles of the one or more drugs.
[0035] Example 1
[0036] Nano-particles of sirolimus were prepared in three different sizes and named Particles A. Particles B, and Particles C. Particles A had an average diameter range of 200 nanometer to 400 nanometer, Particles B had an average diameter range of 400 nanometer to 800 nanometer, and Particles C had an average diameter range of 800 nanometer to 1200 nanometer. Particles A, Particles B, and Particles C were then coated with a blood substance. A solution containing, Particles A, Particles B, and Particles C was prepared. A L605 Cobalt-Chromium alloy stent mounted on a catheter balloon was spray coated with the solution. It was found that some portion of the balloon that was not covered by the stent also got coated with the solution containing Particles A, Particles B, and Particles C.

[00371 During the preliminary studies, it was found that Particles A penetrated up to adventitia layer, Particles B penetrated up to media layer, and Particles C penetrated up to intima layer of the artery. The findings of the preliminary studies also suggested that Particles A were released earliest from the stent followed by Particles B and Particles C respectively.
[0038] Different drugs were used to prepare Particles A, Particles B, and Particles C. Further, Particles A, Particles B, and Particles C were coated on the stent and it was found that the use of different drugs showed promising results in addressing the different therapeutic phases of cell cycle of tissues of blood vessel. It was also found that, the stent manufactured according to above-mentioned method required a low loading dose.
[0039] Various embodiments of the invention provide a DRMD and a method for preparing the same. The invention provides a DRMD that provides for a size-dependent penetration of one or more drugs into one or more layers of tissues of target site to achieve better in-tissue diffusion and in tissue drug release. The invention also provides a DRMD that exhibits enhanced bioavailability and biocompatibility of one or more drugs, which in turn results in a small loading dose thereby minimizing complications such as toxicity, inflammation, and thrombogenicity. Further, the invention provides a DRMD that efficiently addresses the various therapeutic phases of a cell cycle of tissues of a body vessel. Various embodiments of the invention also provide a DRMD that enhances healing process of an affected target site by use of excipientsthat have healing properties.
[0040] Those skilled in the art will realize that the above-recognized advantages and other advantages described herein are merely exemplary and are not meant to be a complete rendering of all of the advantages of the various embodiments of the invention.
[0041] In the foregoing specification, specific embodiments of the invention have been described. However, one of ordinary skill in the art appreciates that various modifications and changes can be made to the invention without deviating from the scope of the invention. Accordingly, the specification is to be regarded in an illustrative rather than a

restrictive sense, and all such modifications are intended to be included within the scope of the invention.