Controlled drug delivery

Abstract

Provided is a drug delivery composition, a method for preparing it, a therapeutic method making use of such a composition, as well as a kit-of-parts that may be used for such preparation or treatment. The drug delivery composition is formed by a mixture of whole blood, typically autologous whole blood withdrawn from the subject to be treated with the drug delivery composition, at least one therapeutically effective active ingredient, and one or more coagulation initiators. The mixture forms a clot that contains the at least one active ingredient, which when being in a desired location in the body of a subject gives rise to release of the active ingredient over time.

Description

[0001] CONTROLLED DRUG DELIVERY

[0002] TECHNOLOGICAL FIELD

[0003] The present disclosure is in the field of drug delivery.

[0004] BACKGROUND ART

[0005] References considered to be relevant as background to the presently disclosed subject matter are listed below:

[0006] - US 9,180,142

[0007] - WO 2019 / 058375

[0008] - WO 2019 / 150355

[0009] - WO 2023 / 144818

[0010] Acknowledgement of the above references herein is not to be inferred as meaning that these are in any way relevant to the patentability of the presently disclosed subject matter.

[0011] GENERAL DESCRIPTION

[0012] The present disclosure provides a drug delivery composition, a method for preparing it, a therapeutic method making use of such a composition, as well as a kit-of- parts that may be used for such preparation or treatment.

[0013] The drug delivery composition is formed by a mixture of whole blood, typically autologous whole blood withdrawn from the subject to be treated with the drug delivery composition, at least one therapeutically effective active ingredient, and one or more coagulation initiators. The mixture forms a clot that contains the at least one active ingredient, which when being in a desired location in the body of a subject gives rise to release of the active ingredient over time, which may be partially a result of the diffusion pattern of the active ingredient out of the blood clot and partially in accordance with the rate of degradation or disintegration of the blood clot.

[0014] The term "active ingredient" denotes an ingredient which exerts a therapeutic, preventive or palliative effect, which may be a local effect at the site of placement of the composition or may also be a systemic effect achieved through the distribution of the drug in the body, through the blood stream, once released from the composition. The active ingredient may be a small molecule drugs, peptides, protein (biologic) drugs, nucleic acid-based drugs, nucleic acid drugs and others. The active ingredient can be in any suitable form, for example a neutral compound, charged compound, solvate, hydrate, salt, enantiomer species or complex. The active ingredient may be in a crystalline form or amorphous. Examples of such active ingredients are immunosuppressants, antibiotics, analgesics, cannabinoids.

[0015] The term "active ingredient". even if not specifically indicated so, should be understood as meaning "at least one active ingredient". And indeed, by some embodiments of this disclosure, the drug delivery composition may include more than one active ingredient, the different active ingredients differing from one another in their chemical nature, release properties from the drug delivery composition, in their physiological or pharmacological activity, in their pharmacokinetic properties, and others.

[0016] The coagulation initiators may be those described in US 9,180,142, WO 2019 / 058375, WO 2019 / 150355 and WO 2023 / 144818, the relevant content of which being incorporated herein by reference. Some exemplary coagulation initiators or combinations of such initiators that may be used in accordance with embodiments of this disclosure, are described in the "Embodiments" section below.

[0017] In some embodiments, the one or more coagulating initiators may comprise an agent that accelerates the blood-clotting cascade, increase firmness of the formed blood coagulant, etc. Examples are kaolin, glass powder, celite powder, ellagic acid, silica powder. As can be appreciated, the teaching of this disclosure is not limited to any specific coagulation initiator or a combination of coagulation initiator. A combination of kaolin and calcium gluconate is a specific, albeit non-limiting example of coagulation initiators.

[0018] The active ingredient-containing blood clot acts as a drug depot that gradually releases the active ingredient through diffusion and / or through the gradual degradation of the blood clot.

[0019] The rate of release of the active ingredient depends, among others, on the properties of the blood clot, e.g. its degree of firmness: a softer blood clot may disintegrate faster than a firmer clot. The firmness of the clot may be controlled by the concentration of the one or more coagulation initiators - a larger concentration may increase firmness and a smaller one decrease it. The rate of disintegration of the blood clot may also be controlled by other factors. One such factor may be the shape of the clot. For example, by some embodiments, increase in the external surface area of the clot may increase the rate of natural disintegration by fibrinolytic agents within the body that cause disintegration of the clot as they would have a larger area to act on. For example, a clot with a small surface area may be spherical, while a clot of the same volume with a larger surface area may be shaped as an elongated cylinder.

[0020] The rate of disintegration by other embodiments may be increased by incorporating fibrinolytic agents into the clot. Examples are proteolytic or fibrinolytic enzymes such as plasmin, trypsin, chymotrypsin; plasminogen or another enzyme precursor, where the enzyme can break down a clot; agents that activate plasminogen such as tissue plasminogen activator (tPA) or urokinase; and others. The rate of disintegration may also be controlled in the opposite direction by incorporating agents that inhibit the fibrinolytic activity.

[0021] The composition of whole blood, coagulating agent and active ingredient may, by some embodiments of this disclosure, be administered, e.g. by injection, prior to its coagulation while still in a flowable state, in which case it coagulates to form a blood clot once in situ. This requires that such administration be done within a relatively short time from mixing, e.g. within 1 to 5 min. Examples of such administration are subcutaneous administration or administration into a joint.

[0022] By another embodiment, the composition is administered after complete coagulation when the clot forms a firm solid or semi-solid block. Such a solidified clotted blood mass may be prepared in a vessel that can serve as a mold that configures the shape of the blood clot. The blood mass that was solidified by clotting may be implemented as such, for example under the skin or in any other desired location in a treated subject body, my surgical or microsurgical techniques known per se. By another embodiment, the solidified, clotted blood mass may be cut down into smaller units and implemented all in the same or different locations. By some embodiments, the cut down units may be sufficiently small to permit their administration by injection.

[0023] By some embodiments of this disclosure, the drug delivery composition may have two or more portions that differ from one another in one or more properties, such as: type or concentration of the active ingredient; and blood clot characteristics, e.g. firmness or disintegration rate characteristics. This may be achieved by forming a first blood clot that comprises (i) a selected amount of a first active ingredient, (ii) a first selected amount of clotted whole blood, and (iii) a selected amount of one or more first coagulation initiators; then contacting the first blood clot with a second mixture that comprises (x) a selected amount of a second active ingredient or of a composing that comprises the second active ingredient, (y) a second selected amount of whole blood, and (z) a selected amount of one or more second coagulation initiators; the second active ingredient being the same or different than the first active ingredient and the second coagulation initiators being the same or different than the first coagulation initiators; and then allowing the second mixture to coagulate and form an integral blood clot with the first blood clot. In the resulting clotted blood mass, one portion is defined by the first blood clot and the other by the blood clot formed from the second mixture.

[0024] One aspect of the present disclosure provides a method for preparing a drug delivery composition. The method comprising (i) mixing a selected amount of an active ingredient or a composition that comprises the active ingredient, (ii) a selected amount of whole blood, typically withdrawn from the subject that is being treated, and (iii) a selected amount of one or more coagulation initiators, including coagulation agents and / or anti- anti -coagulation agents. The active ingredient can be any pharmaceutically or pharmacologically active ingredient and the amount of the active ingredient is selected so as to induce, upon its release from the composition, a desired therapeutic effect. The amount of whole blood and that of the coagulation initiator are selected to yield desired composition properties, for example, according to intended release properties of the active ingredient, e.g. rapid or sustained.

[0025] Another aspect of this disclosure provides a for treating a subject, comprising administering to the subject a drug delivery composition of this disclosure and / or one prepared by the method according to said one aspect. By an embodiment of this aspect the method comprises mixing (i) a selected amount of an active ingredient or a composition that comprises the active ingredient, (ii) a selected amount of whole blood, and (iii) a selected amount of one or more coagulation initiators to obtain a drug delivery mixture; and administering said drug delivery mixture to a desired location within the subject's body.

[0026] Also provides, by a further aspect of this disclosure, is a drug delivery composition, comprising a mixture of (i) selected amount of an active ingredient or a composition that comprises the active ingredient, (ii) selected amount of whole blood, and (iii) selected amount of one or more coagulation initiators. The drug delivery composition may, by an embodiment of this disclosure, be in a flowable form, namely, prior to complete coagulation to be administered in this state, e.g. by injection. The drug delivery composition may, by another embodiment of this disclosure, be in a solidified form after complete coagulation.

[0027] By one embodiment, the drug delivery composition comprises an integral blood clot having a first portion and a second portion. The first portion comprises (i) a selected amount of a first at least one active ingredient, (ii) a first selected amount of clotted whole blood, and (iii) a selected amount of one or more first coagulation initiators. The second portion comprises (i) a selected amount of a second at least one active ingredient, (ii) a second selected amount of clotted whole blood, and (iii) a selected amount of one or more second coagulation initiators. The second at least one active ingredient being the same or different than the first at least one active ingredient and the second coagulation initiators being the same or different than the first coagulation initiators. The two portions differ from one another by at least one of (a) type or concentration of the at least one active ingredient, and (b) blood clot characteristics, e.g. firmness or disintegration rate characteristics.

[0028] The drug delivery composition may be that prepared by the method of said one aspect.

[0029] Also provided by a yet further aspect of this disclosure, is a kit-of-parts for preparing a drug delivery composition for subsequently administering to a subject. Such a kit may comprise: a vessel configured for mixing whole blood with (i) an amount of one or more coagulation initiators effective to cause blood coagulation, and (ii) an amount of active ingredient effective to achieve an intended therapeutic effect, to thereby obtain a therapeutic blood mixture. The kit may also comprise one or more of: (a) a device for administration of the therapeutic blood mixture, either (i) prior to complete coagulation when said mixture is still in a flowable state, or (ii) after complete coagulation and the formation of a therapeutic blood clot, to a site within a body of a subject; (b) one or more blood withdrawal devices for allowing withdrawal of blood from the subject; (c) one or more blood collection receptacles for receiving the blood withdrawn from the subject; (d) an arrangement for the transfer of blood from said receptacle to said vessel; and (e) one or more agents that cause or induce an increase or decrease in rate of disintegration of a blood clot. The coagulation initiators, the one or more active ingredients, and the one or more agents that cause or induce an increase or decrease in rate of disintegration of the blood clot, are typically housed within said vessel.

[0030] It is to be noted that any combination of the described embodiments with respect to any aspect of this present disclosure is applicable also to other apsects. In other words, any aspect of the present disclosure can be defined by any combination of the embodiments described.

[0031] Embodiments of the different aspects of this disclosure, are described below.

[0032] EMBODIMENTS

[0033] The following numbered paragraphs describe optional, non-limiting embodiments of the present disclosure that are meant to add to the above General Description. Any combination of these embodiments may be applicable in accordance with this disclosure.

[0034] 1. A method for preparing a drug delivery composition, comprising: mixing (i) a selected amount of at least one active ingredient or a composition that comprises the at least one active ingredient, (ii) a selected amount of whole blood, and (iii) a selected amount of one or more coagulation initiators.

[0035] 2. The method of embodiment 1, wherein the one or more coagulation initiators comprise a coagulation agent or any anti-anti -coagulation agent.

[0036] 3. The method of embodiment 2, wherein the one or more coagulation initiators comprise one or both of a clay, such as kaolin, or a calcium salt such as calcium gluconate.

[0037] 4. The method of embodiment 3, wherein the coagulation initiators comprise kaolin and calcium salt.

[0038] 5. The method of embodiment 4, wherein the kaolin and the calcium salt are introduced in the form of a finely ground particulate matter or a powder.

[0039] 6. The method of any one of embodiments 3-5, wherein the coagulation inducer comprises kaolin and at least one of the following applies: (i) the amount of kaolin is in the range of about 0.6 mg - 3.1 mg of kaolin powder for every 1 ml of whole blood, and (ii) the particle-size distribution D50 of the kaolin powder is less than 20p.

[0040] 7. The method of embodiment 6, wherein the kaolin concentration (namely amount of for each 1 ml of whole blood) or its particle size has the characteristics as described in WO 2023 / 144818, the content of which is being incorporated herewith by reference. 8. The method of any one of embodiments 3-7, wherein the coagulation inducer comprises calcium gluconate and at least one of the following applies: (i) the calcium gluconate is introduced in the form of a powder and the particle-size distribution D50 of the calcium gluconate powder is in the range of about 50p-200p, and (ii) the amount of calcium gluconate is in the range of about 2.5 mg - 8.1 mg for every 1 ml of whole blood.

[0041] 9. The method of embodiment 8, wherein the calcium gluconate concentration (namely amount of for each 1 ml of whole blood) or its particle size has the characteristics as described in WO 2023 / 144818, the content of which is being incorporated herewith by reference.

[0042] 10. The method of any one of embodiments 1-9, wherein the composition is intended for administration prior to complete coagulation when said composition is still in a flowable form.

[0043] 11. The method of embodiment 10, wherein the administration is by injection.

[0044] 12. The method of any one of embodiment 1 -9, wherein the composition is intended for administration as a blood clot after complete coagulation.

[0045] 13. The method of any one of embodiments 12, comprising: mixing (i) a selected amount of an at least one active ingredient or a composition that comprises the at least one active ingredient , (ii) a selected amount of whole blood, and (iii) a selected amount of one or more coagulation initiators, to obtain a whole blood mixture; permitting the whole blood mixture to coagulate and form a clot-based drug delivery composition.

[0046] 14. The method of embodiment 13, wherein the mixing is performed in a vessel and the whole blood mixture is permitted to clot therein.

[0047] 15. The method of embodiment 13 or 14, wherein the clotted whole blood mixture is cut into several pieces each intended for separate administration to a site within a body of a treated subject.

[0048] 16. The method of any one of embodiments 1-15, wherein the composition is intended for subcutaneous administration.

[0049] 17. The method of any one of embodiments 1-16, wherein the composition is intended for administration into a joint. 18. The method of embodiment 17, wherein the composition comprises an anti-inflammatory or analgesics active ingredient.

[0050] 19. The method of any one of embodiments 14-18, comprising forming a first blood clot that comprises (i) a selected amount of a first at least one active ingredient, (ii) a first selected amount of clotted whole blood, and (iii) a selected amount of one or more first coagulation initiators; contacting the first blood clot with a second mixture that comprises (x) a selected amount of a second at least one active ingredient or of a composing that comprises the second at least one active ingredient , (y) a second selected amount of whole blood, and (z) a selected amount of one or more second coagulation initiators; the second at least one active ingredient being the same or different than the first at least one active ingredient and the second coagulation initiators being the same or different than the first coagulation initiators; and allowing the second mixture to coagulate and form an integral blood clot with the first blood clot, the integral blood clot having two portions of different properties, one defined by the first blood clot and the other by the blood clot formed from the second mixture, the different properties comprising at least one of: (a) type or concentration of the active ingredient, and (b) blood clot characteristics.

[0051] 20. The method of embodiment 19, wherein the blood clot characteristics are rate of disintegration.

[0052] 21. The method of any one of embodiments 1-20, wherein the intended administration comprises injecting the composition in a defined subcutaneous location for local delivery of the active ingredient.

[0053] 22. The method of embodiment 21 , wherein said active ingredient is lidocaine and the administration is performed into a joint.

[0054] 23. The method of any one of embodiments 1-22, wherein the active ingredient is a biological drug.

[0055] 24. The method of any one of embodiments 1-23, wherein said mixing comprises adding one or more agents that cause or induce an increase or decrease in rate of disintegration of a blood clot.

[0056] 25. The method of any one of embodiments 1-24, wherein the whole blood is an autologous whole blood of a treated subject. 26. A method for treating a subject, comprising administering to the subject a drug delivery composition of the any one of embodiments 1-25.

[0057] 27. A method for delivering a drug to a subject, comprising: mixing (i) a selected amount of an at least one active ingredient or a composition that comprises the at least one active ingredient, (ii) a selected amount of whole blood, and (iii) a selected amount of one or more coagulation initiators to obtain a drug delivery mixture; and administering said drug delivery mixture to a desired location within the subject's body.

[0058] 28. The method of embodiment 27, wherein the drug delivery mixture is the drug delivery composition of any one of embodiments 1-25.

[0059] 29. The method of embodiment 27 or 28, wherein the whole blood is an autologous whole blood of a treated subject.

[0060] 30. The method of any one of embodiments 27-29, wherein said administration comprises subcutaneous injection.

[0061] 31. The method of any one of embodiments 26-30, wherein said active ingredient is lidocaine and the administration is into the subject's joint, e.g. the knee.

[0062] 32. The method of any one of embodiments 26-31, wherein the active ingredient is a biological drug.

[0063] 33. The method of any one of embodiments 26-32, wherein said mixing comprises adding one or more agents that cause or induce an increase or decrease in rate of disintegration of a blood clot within the body.

[0064] 34. A drug delivery composition, comprising: a mixture of (i) selected amount of an at least one active ingredient or a composition that comprises the at least one active ingredient, (ii) selected amount of whole blood, and (iii) selected amount of one or more coagulation initiators.

[0065] 35. The drug delivery composition of embodiment 34, prepared by the method of any one of embodiments 1-25.

[0066] 36. The drug delivery composition of embodiment 34 or 35, in a flowable state prior to complete coagulation.

[0067] 37. The drug delivery composition of embodiment 34 or 35, in a coagulated state. 38. The drug delivery composition of any one of embodiments 34-37, wherein the whole blood is an autologous whole blood of a treated subject.

[0068] 39. The drug delivery composition of any one of embodiments 34-38, comprising an integral blood clot having a first portion and a second portion; the first portion comprises (i) a selected amount of a first at least one active ingredient , (ii) a first selected amount of clotted whole blood, and (iii) a selected amount of one or more first coagulation initiators; and the second portion comprises (i) a selected amount of a second at least one active ingredient , (ii) a second selected amount of clotted whole blood, and (iii) a selected amount of one or more second coagulation initiators; the second at least one active ingredient being the same or different than the first at least one active ingredient and the second coagulation initiators being the same or different than the first coagulation initiators; the two portions differing from one another by at least one of (a) type or concentration of the at least one active ingredient, and (b) blood clot characteristics.

[0069] 40. The drug delivery composition of any one of embodiments 34-39, wherein said mixture further comprises one or more agents that cause or induce an increase or decrease in rate of disintegration of a blood clot within the body.

[0070] 41. A kit for preparing drug delivery composition for delivering at least one active ingredient to a subject, comprising: a vessel configured for mixing whole blood with (i) an amount of one or more coagulation initiators effective to cause blood coagulation, and (ii) an amount of at least one active ingredient effective to achieve an intended therapeutic effect, to thereby obtain a therapeutic blood mixture.

[0071] 42. The kit of embodiment 41 , wherein said one or more coagulation initiators and said at least one active ingredient are housed within said vessel.

[0072] 43. The kit of embodiment 41 or 42, comprising: a device for administration of the therapeutic blood mixture, either (i) prior to complete coagulation when said mixture is still in a flowable state, or (ii) after complete coagulation and the formation of a therapeutic blood clot, to a site within a body of a subject.

[0073] 44. The kit of any one of embodiments 41-43, comprising one or more of: one or more blood withdrawal devices for allowing withdrawal of blood from the subject; one or more blood collection receptacles for receiving the blood withdrawn from the subject; and an arrangement for the transfer of blood from said receptacle to said vessel (e.g. a syringe and / or a device of the kind disclosed in US 2023 / 158201, the content of which is being incorporated herewith by reference).

[0074] 45. The kit of any one of embodiments 41-44, further comprising one or more agents that cause or induce an increase or decrease in rate of disintegration of the blood clot.

[0075] 46. The kit of embodiment 45, wherein said one or more agents are housed within said vessel.

[0076] 47. The kit of any one of embodiments 41-44 for use in the method according to any one of embodiments 1-33.

[0077] BRIEF DESCRIPTION OF THE DRAWINGS

[0078] In order to better understand the subject matter that is disclosed herein and to exemplify how it may be carried out in practice, embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which:

[0079] Fig. 1 is a schematic illustration of a delivering device for preparing and delivering the drug delivery composition of the present disclosure.

[0080] Figs. 2A-2B are schematic illustrations of a cross-sectional view of non-limiting examples of two embodiments of a drug delivery composition according to an aspect of the present disclosure.

[0081] DETAILED DESCRIPTION

[0082] The following figures are provided to exemplify embodiments and realization of the invention of the present disclosure.

[0083] Fig. 1 is a schematic illustration of a delivering tool that comprises the drug delivery composition of the present disclosure. In this example, the delivering tool 101 is a syringe that receives into its tube space a mixture 102 of whole blood, active ingredient, and coagulation initiators. While the mixture is still in a flowable state, namely when the coagulation process is not completed, the mixture can be injected into any desired target location of to form a clot in-vivo, to permit a gradual local delivery of the active ingredient. The injection site may, for example, be a subcutaneous or sub-dermal administration.

[0084] The syringe 101 may, by some embodiments, house one or coagulation inducers and at least one active ingredient which become mixed with the whole blood mass once introduced into the syringe 101 to form mixture 102.

[0085] Optionally, the mixture 102 further includes one or more agents that affect the rate of disintegration of the clot, of the kind described above. The result, depending on the nature of such one or more agents, causes an increase or decrease of the rate of disintegration of the clot, and hence a corresponding increase or decrease the delivery rate of the active ingredient.

[0086] While the mixture 102 is delivered while in a flowable state and is coagulated in situ, by other embodiments a blood clot-based drug deliver composition is prepared ex vivo and then introduced into the body. The clot may be formed in a vessel that may a priori contain the one or more coagulating agents, the at least one active ingredient and the optional one or more agents that cause or induce an increase or decrease in rate of disintegration of a blood clot.

[0087] Reference is being made to Figs. 2A-2B, which are cross-sectional views of nonlimiting examples of two embodiments of clotted drug delivery composition of the present disclosure. Fig. 2A shows a coagulated form of a drug delivery composition 200 that comprises a mixture 202 of whole blood, active ingredient, coagulation initiators and the optional one or more agents that cause or induce an increase or decrease in rate of disintegration of a blood clot. The drug delivery composition 200 is homogeneous and the concentration of the active ingredient is generally uniform throughput the entire composition. Furthermore, the characteristics of the blood clot that supports the active ingredient is generally homogeneous.

[0088] The drug delivery composition that is shown has a general circular cross-section, e.g. may have the general shape of a sphere or a hemisphere, but may also, by other embodiments, have other configurations, e.g. that of an elongated cylinder.

[0089] Fig 2B shows another example of a drug delivery composition 200, in which there are two distinctive portions 202A and 202B, differing from one another by at least one of (i) active ingredient type or concentration, and (ii) blood clot characteristics. The latter may be affected by the content of coagulation initiators that were used to produce the composition which can affect firmness and hence the rate of disintegration. For example, the outer portion 202B may be designed to have a faster rate of clot disintegration so as to expose the core portion 202A after a time, the core 202A having a lower disintegration rate . Portions 202A and 202B may also have different types or concentrations of the active ingredient, for example lower concentration of active ingredient in portion 202B as compared to that of portion 202B. Such a composition may be prepared, for example, as generally described above in the method of embodiments Nos. 19 and / or 20.

[0090] The drug delivery compositions exemplified in Figs. 2A-2B can be prepared in coagulation mold of the desired shape, e.g. spherical, hemispherical, cylindrical, flat, etc.

[0091] The coagulation mold receives the mixture of whole blood, active ingredient, and coagulation initiators to form the drug delivery composition, which can be implanted or injected into a desired location.

Claims

CLAIMS:

1. A method for preparing a drug delivery composition, comprising: mixing (i) a selected amount of an at least one active ingredient or a composition that comprises the at least one active ingredient, (ii) a selected amount of whole blood, and (iii) a selected amount of one or more coagulation initiators.

2. The method of claim 1, wherein the composition is intended for administration to be carried out when said composition is still in a flowable form.

3. The method of claim 1, comprising: allowing the mixture to coagulate ex-vivo and to form a blood clot that comprises the at least one active ingredient, and administering the blood clot to the subject.

4. The method of claim 3, comprising: forming a first blood clot that comprises (i) a selected amount of a first at least one active ingredient, (ii) a first selected amount of clotted whole blood, and (iii) a selected amount of one or more first coagulation initiators; contacting the first blood clot with a second mixture that comprises (i) a selected amount of a second at least one active ingredient or of a composing that comprises the second at least one active ingredient , (ii) a second selected amount of whole blood, and (iii) a selected amount of one or more second coagulation initiators; the second at least one active ingredient being the same or different than the first at least one active ingredient and the second coagulation initiators being the same or different than the first coagulation initiators; and allowing the second mixture to coagulate and form an integral blood clot with the first blood clot, the integral blood clot having two portions of different properties of at least one of: (a) type or concentration of the at least one active ingredient, and (b) blood clot characteristics.

5. The method of any one of claims 2-4, wherein the intended administration comprises injecting the composition in a defined subdermal location to result in local delivery of the at least one active ingredient.

6. The method of claim 5, wherein said at least one active ingredient is lidocaine and the administration is performed into a joint.

7. The method of any one of claims 1-6, wherein the at least one active ingredient is a biological drug.

8. The method of any one of claims 1-7, wherein said mixing comprises adding one or more agents that cause or induce an increase or decrease in rate of disintegration of a blood clot within the body.

9. The method of any one of claims 1-8, wherein the whole blood is an autologous whole blood of a treated subject.

10. A method for delivering a drug to a patient, comprising: mixing a selected amount of an at least one active ingredient or a composition that comprises the at least one active ingredient with a selected amount of whole blood and with a selected amount of one or more coagulation initiators to obtain a drug delivery mixture; administering said drug delivery mixture to a desired location within the patient body.

11. A drug delivery composition, comprising: a mixture of (i) selected amount of at least one active ingredient or a composition that comprises the at least one active ingredient, (ii) selected amount of whole blood, and (iii) selected amount of one or more coagulation initiators.

12. The drug delivery composition of claim 11, in a flowable state prior to complete coagulation.

13. The drug delivery composition of claim 11, in a coagulated state.

14. The drug delivery composition of any one of claims 11-13 wherein the whole blood is an autologous whole blood of a treated subject.

15. The drug delivery composition of any one of claims 11-14, comprising an integral blood clot having a first portion and a second portion; the first portion comprises (i) a selected amount of a first at least one active ingredient, (ii) a first selected amount of clotted whole blood, and (iii) a selected amount of one or more first coagulation initiators; and the second portion comprises (i) a selected amount of a second at least one active ingredient , (ii) a second selected amount of clotted whole blood, and (iii) a selected amount of one or more second coagulation initiators; the second at least one active ingredient being the same or different than the first at least one active ingredient and the second coagulation initiators being the same or different than the first coagulation initiators;the two portions differing from one another by at least one of (a) type or concentration of the at least one active ingredient, and (b) blood clot characteristics.

16. The drug delivery composition of any one of claims 11-15, wherein said mixture further comprising one or more agents that cause or induce an increase or decrease in rate of disintegration of a blood clot within the body.

17. A kit for preparing drug delivery composition for delivering an at least one active ingredient to a subject, comprising: a vessel configured for mixing whole blood with (i) an amount of one or more coagulation initiators effective to cause blood coagulation, and (ii) an amount of at least one active ingredient effective to achieve an intended therapeutic effect, to thereby obtain a therapeutic blood mixture.

18. The kit of claim 17, comprising: a device for administration of the therapeutic blood mixture, either (i) prior to complete coagulation when said mixture is still in a flowable state, or (ii) after complete coagulation and the formation of a therapeutic blood clot, to a site within a body of a subject.

19. The kit of claim 17, comprising one or more of: one or more blood withdrawal devices for allowing withdrawal of blood from the subject; one or more blood collection receptacles for receiving the blood withdrawn from the subject; and an arrangement for the transfer of blood from said receptacle to said vessel.

20. The kit of claim 19, further comprising one or more agents that cause or induce an increase or decrease in rate of disintegration of a blood clot within the body.

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