Methods and kits for treating abnormal sinusoidal spaces - Patents.com

Abstract

The present disclosure provides a method and kit for treating an abnormal cavity space in a subject, such as a fistula, e.g., an anal fistula or stoma space. For example, the abnormal cavity space may be an anal fistula, a stoma opening, or a pilonidal sinus. The method utilizes autologous blood from the subject, introduces it into the abnormal cavity space, and allows it to coagulate within the abnormal cavity space, thereby forming a coagulated blood mass, or clot, within the cavity space and facilitating the healing process of the abnormal cavity space. Healing may be a complete or partial closure or reduction in the size or volume of the space, or the formation of healthy tissue within the previously abnormal cavity space.

Description

[Technical field]

[0001] The present disclosure relates to the field of treatment of abnormal sinus spaces, particularly fistulas or anal fistulas, in a subject. [Background technology]

[0002] The following references are considered relevant background to the subject matter of this disclosure: -International Publication No. 2019 / 058373 -International Publication No. 2019 / 058375 -U.S. Patent No. 9,180,142

[0003] The acknowledgement of the above references herein should not be inferred as meaning that they are in any way relevant to the patentability of the subject matter of the present disclosure. Summary of the Invention

[0004] The present disclosure provides a method and kit for treating an abnormal cavity space in a subject, such as a fistula, e.g., an anal fistula or stoma space. The term "abnormal cavity space" in the context of the present disclosure should be interpreted as an abnormal cavity formed in a human or non-human animal due to or as a result of a specific medical condition. For example, the abnormal cavity space may be an anal fistula, a stoma opening, or a pilonidal sinus. The method utilizes autologous blood from the subject, introduces it into the abnormal cavity space, and allows it to coagulate within the abnormal cavity space, thereby forming a coagulated blood mass, i.e., a blood clot, within the cavity space and facilitating the healing process of the abnormal cavity space. Healing may be a complete or partial closure or reduction in the size or volume of the space, or the formation of healthy tissue within the previously abnormal cavity space.

[0005] The abnormal cavity space treated according to some embodiments of the present disclosure includes at least one opening on the external surface of the body. That is, the cavity space is accessible through an opening formed in a portion of the subject's skin. According to other embodiments, the abnormal cavity space may open into an internal body cavity, for example, a fistula between two tubular organs (e.g., between the colon and the urethra).

[0006] Thus, a first aspect of the disclosure provides a method of treating an abnormal cavitary space in a subject. The method includes (i) obtaining or harvesting whole blood from a subject. This step can be performed by any method known in the art. The method further includes (ii) mixing the subject's blood with one or more clotting agents or anti-anticoagulants to initiate the blood's clotting process. Then, (iii) introducing, e.g., injecting, the blood containing the clotting agent into said cavitary space before the blood is fully coagulated, and (iv) allowing the blood to clot in said abnormal cavitary space until the blood is fully coagulated and a clot is formed in the abnormal cavitary space. It should be noted that when referring to the term "before the blood is fully coagulated", it means that the clotting process has been initiated but the blood is still in a flowable state, e.g., by injection, to flow into the abnormal cavitary space and complete clotting therein, i.e., to coagulate and form a clot in the abnormal cavitary space. The clot may be maintained in the space into which it was injected for a period of time, e.g., hours or days, or may be maintained throughout the entire healing process. The clotted blood clot within the abnormal sinus space may be absorbed, naturally decomposed, naturally pushed out of the healing sinus space, or removed after a period of time.

[0007] In some embodiments of this method, the method includes the step of withdrawing whole blood from the subject and mixing it with an anticoagulant prior to introducing the blood into the cavity space to be treated, which allows for control of the clotting process, e.g., by the nature of the anticoagulant or its concentration, to fine-tune the clotting time and the physical properties of the resulting clotted blood.

[0008] In some embodiments of this method, the anticoagulant is selected from the group consisting of ACD-A (Anticoagulant Citrate Dextrose, Solution A), EDTA (ethylenediaminetetraacetic Acid), EGTA (ethylene glycol tetraacetic acid), citrate, heparin, and oxalate.

[0009] In some embodiments, the method further comprises the step of forming a sinus by sealing one or more openings of the cavity space, e.g., the distal opening of the fistula, if said cavity space has two or more openings, e.g., a fistula, i.e., keeping only one opening open. This step is performed at any time prior to (iii) above. In some embodiments, the method further comprises the step of (iv) applying a medical dressing or seal to the opening of the cavity space to prevent leakage of blood from the abnormal cavity space or sinus, thereby ensuring clotting of blood in the cavity space.

[0010] In some embodiments, the method further comprises the step of sealing one of the openings of the abnormal cavity space by expanding the expandable element to block one of the openings. For example, in the case of an anal fistula, such expansion of the expandable element may be performed in the rectum, the walls of the expandable element thereby sealing the opening of the fistula into the rectal lumen. After the opening is sealed by the expanded element, the clotting blood is introduced into the abnormal cavity space through the unblocked opening. In some cases, the expandable element may be maintained in situ for a limited time, e.g., after the blood has been allowed to clot to a sufficient extent in the abnormal cavity space, the expandable element may be deflated and withdrawn. This is relevant, for example, in the case of an anal fistula, where one of the openings of the anal fistula is in the wall of the rectal lumen and blood is introduced through an opening formed in the external skin near the anus. Thus, the expandable element is introduced through the rectum in a non-inflatable state, and once in place, the expandable element is expanded to an expanded state to seal the opening to the rectal lumen, and only after such sealing is clotting blood introduced through the external opening. The blood is then allowed to coagulate within the cavity space of the fistula, for example for a few minutes, after which the expandable element can be deflated and removed. Once the blood has sufficiently coagulated, the expandable element may not need to retain the clotting agent within the fistula, and the expandable element is deflated to a non-inflated state and withdrawn through the rectum, with the clotted blood remaining within the cavity space of the fistula.

[0011] According to some embodiments of the method, a medical dressing or seal is applied to the opening of the treated cavity space, which may be immediately after introducing the clotting blood into the cavity space, or after a period of time, such as after a period of 3 to 15 minutes from introduction, or after a period of 1, 2, 3, 4, 5, 6, 7, 8 to 10, 11, 12, 13, 14, 15, 16 minutes, or after a period of about 9 minutes. Note that this period is typically a time frame that allows blood to clot within the abnormal cavity space. In some embodiments, this time frame may be less than 10, 9, 8, 7, 6, 5, 4, 3, 2, or sometimes less than 1 minute.

[0012] The term "about" should be understood as up to a 20% deviation from the specified value, for example, a period of about 10 minutes refers to any period between 8 and 12 minutes.

[0013] In some embodiments of this method, the one or more coagulants are in the form of a liquid or a powder.

[0014] In some embodiments of this method, the one or more coagulants or anticoagulants are selected from the group consisting of kaolin, Ca 2+ (e.g., in the form of calcium salts such as calcium gluconate), Mg 2+ , negatively charged lipids (PL) and protamine sulfate.

[0015] In some embodiments of this method, (ii) comprises first mixing the blood with calcium gluconate, and then mixing the mixture of blood and calcium gluconate with kaolin.

[0016] In some embodiments of this method, the cavity space is a fistula.In some embodiments of this method, the fistula is a fistula-in-ano.

[0017] In some embodiments of this method, the hollow space is a cavity.

[0018] In some embodiments of this method, the cavity space is a pilonidal sinus.

[0019] In some embodiments of the method, blood is introduced or injected into the abnormal cavity space with a predetermined injection profile, which includes first injecting blood into the distal end of the cavity space until the entire space is filled, i.e., until blood fills the space up to its proximal end. This profile can prevent expansion of the abnormal cavity space, e.g., a fistula, if it is flexible, and ensure that the injected blood fills the entire volume of the abnormal cavity space.

[0020] In some embodiments of this method, elements (ii) and (iii) of the method (defined above) are performed simultaneously, i.e., blood is mixed with one or more coagulants or anti-anticoagulants while the blood is being introduced or injected into the abnormal cavitary space.

[0021] In some embodiments of this method, prior to (iii), the method further comprises sealing the opening of the abnormal cavity space with a seal having an inlet, followed by (iii), wherein the introducing is via the inlet.

[0022] In some embodiments of the method, at least one of the openings of the abnormal cavity space is formed on the outer surface part of the subject's body. Thus, the at least one opening is available for introducing clotting blood into the abnormal cavity space without the need to penetrate the body. Depending on the site of the abnormal cavity space to be treated, the opening can be formed, for example, in the rectal part, the abdomen, or any other exposed part on the subject's body.

[0023] In some embodiments of the method, the cavity space is an abdominal space. The abdominal space may be formed as a result of a stoma or stoma reversal surgery, and blood may be introduced through a stoma opening that constitutes the opening of the abnormal cavity space. In a stoma reversal surgery, the clotting blood introduced into the abdominal space contacts the stoma opening and also the reanastomosed intestinal ends that were separated during the stoma surgery. The blood then coagulates at the tissue to be healed, i.e., the stoma opening and the adhesive interface between the two reanastomosed intestinal ends, facilitating the healing process.

[0024] Yet another aspect of the present disclosure provides a kit or system of parts for use in treating an abnormal sinus space or cavity in a subject, the kit or system including one or more blood draw devices for drawing blood from the subject, one or more blood collection containers for receiving the drawn blood from the subject, a clotting assembly configured to mix the drawn blood with one or more clotting agents to initiate the clotting process of the drawn blood, and an applicator for introducing the clotting blood into the sinus space.

[0025] In some embodiments of the kit or system, one or more of the collection vessels is a vacuum tube.

[0026] In some embodiments of the kit or system, the clotting assembly includes a housing for receiving the drawn blood and mixing it with one or more clotting agents or anti-anticoagulants.

[0027] In some embodiments, the kit further comprises one or more anticoagulants to mix with the collected blood to prevent its natural clotting process and to enable controllably inducing its clotting at a desired time.

[0028] In some embodiments of the kit, one or more anticoagulants are contained within the one or more blood collection containers.

[0029] In some embodiments of the kit, the anticoagulant is selected from the list consisting of ACD-A (anticoagulant citrate dextrose, solution A), EDTA (ethylenediaminetetraacetic acid), EGTA (ethylene glycol tetraacetic acid), citrate, heparin, and oxalate.

[0030] In some embodiments of the kit, the one or more coagulants or anticoagulants include kaolin, Ca 2+ (e.g., in the form of calcium salts such as calcium gluconate), Mg 2+ , negatively charged lipids (PL) and protamine sulfate.

[0031] In some embodiments, the kit further comprises a seal for sealing the opening of the abnormal cavity space, the seal comprising an inlet for allowing clotting blood to be infused through the seal into the abnormal cavity space.

[0032] In some embodiments of the kit, the abnormal cavity space is a fistula. In some embodiments of the kit, the fistula is a fistula-in-ano.

[0033] In some embodiments of the kit, the abnormal cavity space is a sinus.

[0034] It should be noted that the term "sinus" refers to any pouch or cavity in an organ or tissue, or an abnormal cavity or passageway caused by destruction of tissue.

[0035] In some embodiments, the kit is intended for use in a method for treating an abnormal sinus space or cavity in a subject, the method comprising: (i) drawing or obtaining whole blood from a subject; (ii) mixing the subject's blood with one or more coagulants or anti-anticoagulants; (iii) introducing blood containing a clotting agent into said cavity space before the blood is completely coagulated; (iv) allowing the blood to clot within the abnormal cavity space until the blood completely coagulates and a blood clot is formed within the abnormal cavity space.

[0036] In some embodiments, the kit is intended for use in any of the above embodiments of the method. [Brief description of the drawings]

[0037] In order to better understand the subject matter disclosed herein, and to illustrate 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:

[0038] [Figure 1A]FIG. 2 is a schematic diagram illustrating different stages of a non-limiting example of a method according to one aspect of the present disclosure. [Figure 1B] FIG. 2 is a schematic diagram illustrating different stages of a non-limiting example of a method according to one aspect of the present disclosure. [Figure 1C] FIG. 2 is a schematic diagram illustrating different stages of a non-limiting example of a method according to one aspect of the present disclosure. [Figure 1D] FIG. 2 is a schematic diagram illustrating different stages of a non-limiting example of a method according to one aspect of the present disclosure. [Figure 2A] 1 is a flow diagram of a non-limiting example of different embodiments of a method according to an aspect of the present disclosure. [Figure 2B] 1 is a flow diagram of a non-limiting example of different embodiments of a method according to an aspect of the present disclosure. [Figure 3A] 1 is a schematic diagram showing different stages of a procedure for treating anal fistula. [Figure 3B] 1 is a schematic diagram showing different stages of a procedure for treating anal fistula. [Figure 3C] 1 is a schematic diagram showing different stages of a procedure for treating anal fistula. [Figure 3D] 1 is a schematic diagram showing different stages of a procedure for treating anal fistula. [Figure 3E] 1 is a schematic diagram showing different stages of a procedure for treating anal fistula. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0039] The method of the present disclosure is aimed at treating abnormal sinus spaces present in a subject, such as an anal fistula. The method first requires obtaining whole blood from a subject having an abnormal sinus space to be treated. This is done by drawing blood from the subject by any known method. After drawing the blood, it is common to mix it with an anticoagulant so that the blood can be stored in an unclotted liquid form until it is desired to coagulate the blood to form a clot. Reference is now made to Figures 1A-1C, which are schematic diagrams illustrating different stages of an embodiment of a method according to one aspect of the present disclosure after blood has been drawn from a patient. Figure 1A shows a coagulation assembly 102, which includes a sealed blister 104 enclosing a sterile volume 106 for receiving blood drawn from a subject. The sealed blister 104 is formed from a blood inlet portion 108, which may be transparent or translucent to allow visualization of the process, and a coagulant-containing surface 110 that holds a liquid or powder form of one or more coagulants or anti-anticoagulants. By using a piercing element 111, e.g. a syringe with a suitable needle, the blood inlet portion 108 is pierced in two different positions to form two openings, as seen in FIG. 1A, which allows blood to be introduced into the sterile volume 106 through the first opening while air escapes through the second opening. The collected blood is then injected into the sterile volume 106, and a coagulant or anti-anticoagulant is mixed with the subject's blood to initiate the clotting process, as illustrated in FIG. 1B. The mixing can be enhanced by shaking the clotting assembly 102 after sealing the opening of the blood inlet portion 108 to prevent blood leakage during shaking. The blister 104 is then opened, for example, by removing the sealing base 112 at the bottom of the blister 104, as illustrated in FIG. 1C, or by piercing the blood inlet portion 108 and drawing the clotting blood into a syringe. The process then involves aspirating the clotting blood from the blister and injecting it into the abnormal cavity space, such as a fistula, or into a sinus cavity if one or more of the openings of the abnormal cavity space have been sealed, such as by a suture procedure.This is illustrated in FIG. 1D, which shows blood containing a coagulant or anti-anticoagulant stored in a syringe 114 being injected into the fistula FIS where it is allowed to clot.

[0040] Reference is now made to Figures 2A-2B, which are flow diagrams illustrating different embodiments of a method according to one aspect of the present disclosure. The method illustrated in Figure 2A includes a step 250 of drawing whole blood from a subject having an abnormal cavity space to be treated, such as a fistula or anal fistula. The method further includes a step 252 of mixing the drawn blood with one or more coagulants or anti-anticoagulants. The method then includes a step 254 of introducing the blood and coagulant mixture into the abnormal cavity space. This is done while the blood is still in a flowable state, i.e., before it has completely coagulated. While the blood is in the cavity space, the method includes a step 256 of allowing the blood to coagulate within the abnormal cavity space, thereby forming a blood clot within the abnormal cavity space.

[0041] Reference is now made to Figure 2B, which differs from Figure 2A in that it includes drawing whole blood from a subject (250) and then mixing the blood with one or more anticoagulants, thereby inhibiting the blood's natural clotting process and allowing the clotting process to be controllably induced at desired times.

[0042] It should be noted that if it is necessary to seal one or more openings of the abnormal cavity space, the method further includes a step of sealing the one or more openings to form a cavity into which clotting blood is introduced.

[0043] Reference is now made to Figures 3A-3E, which are schematic diagrams illustrating a procedure for treating a fistula in ano according to the present disclosure. Figure 3A shows an initial pathology of a subject consisting of an abnormal cavity space formed by an abdominal fistula in ano FIS. First, as shown in Figure 3B, a sterile liquid SL is introduced from one opening of the fistula in ano FIS to wash the fistula in ano FIS. Typically, the liquid is introduced through the first opening of the fistula in ano and is drained through the second opening. Next, as seen in Figure 3C, an inflatable / contractable element 316 is introduced through the rectum RM when in a contracted state. Once positioned near an opening OP accessible only through the rectum, the inflatable / contractable element 316 is expanded to its expanded state, as shown in Figure 3D, and coagulated whole blood 318 taken from the subject is introduced through the non-sealing opening NSO of the fistula in ano FIS. The whole blood is allowed to clot sufficiently within the stoma FIS before the expandable / contractible element 316 is contracted to its contracted state and withdrawn via the rectum RM. EXAMPLES

[0044] Below are examples of clinical trials based on various aspects of the present invention.

[0045] Example 1 - Autologous whole blood clot treatment in patients with anal fistula Objective: Anal fistula is a chronic inflammatory process that usually does not heal spontaneously, so surgery remains the definitive treatment. High recurrence rates of fistulas and potential risk of fecal incontinence remain major problems after surgery.

[0046] ActiGraft is an autologous blood clot generated from the patient's own peripheral blood, forming a fibrin clot that promotes cellular regeneration through physical and biological mechanisms. ActiGraft has been shown to promote chronic wound healing from the stagnant phase of inflammation to the proliferative phase, resulting in cellular proliferation, wound bed granulation tissue formation, and wound closure.

[0047] Methods: Twenty-nine patients with chronic anal fistula underwent surgical procedures including fistula irrigation and debridement, and suturing the internal, rectal side, and opening. A water leakage test was performed. After the procedure, 18 mL of blood was collected from the patients, mixed with kaolin and calcium gluconate, and immediately injected into the wound of the fistula tract to block the sinus and allow the blood to coagulate internally. Fistula healing was verified by visual evaluation and MRI 3 months after application.

[0048] Results: At the time of this report, eight subjects had completed the six-month follow-up, while all 19 other subjects are ongoing. An interim analysis of the per protocol population showed that ActiGraft treatment resulted in complete cure, as confirmed by MRI, in seven of eight patients who had completed the six-month follow-up. Interestingly, one of the seven patients who was cured was a patient with Crohn's disease, demonstrating the dramatic effect of ActiGraft on this subpopulation of patients.

[0049] Conclusions: ActiGraft was found to be safe and effective in treating patients with anal fistula, including those with Crohn's disease, achieving complete healing 3 months after surgery.

[0050] Example 2 - Safety and Efficacy of Autologous Whole Blood Clot Therapy in the Pilonidal Sinus Following Minimally Invasive Surgery Objective: Pilonidal disease is a common condition affecting young patients worldwide. It most commonly occurs in the hair follicles of the sacrococcygeal birth cleft and causes a foreign body reaction leading to the formation of a midline depression; this condition can cause infection, significant discomfort, pain, immobility, and reduced work productivity in otherwise healthy young adults. The common treatment for pilonidal disease is surgical resection of the sinus tract, which involves surgical risks.

[0051] ActiGraft, an autologous blood clot, has been found to be safe and effective in healing post-operative and chronic wounds of the skin. Blood clots are the body's natural and optimal temporary wound matrix, acting as a temporary substrate onto which cells can migrate and promote local tissue regeneration. Blood clot treatment of pilonidal sinus with minimally invasive surgery acts not only as a temporary substrate but also as a regenerative tissue that can seal the sinus cavity and result in the formation of new granulation tissue and re-epithelialization, thus shortening healing times and preventing sinus recurrence and complications.

[0052] Methods: Forty-three patients with pilonidal sinus underwent minimally invasive trephine surgery. Immediately after the procedure, 18 mL of blood was collected, mixed with kaolin and calcium gluconate, and immediately injected into the sinus cavity to allow the blood to coagulate internally and form a clot. Pilonidal sinus healing was visually verified 12 weeks postoperatively.

[0053] Results: An interim analysis was performed on the per protocol population. Twenty-five patients completed the 12-week follow-up, 13 patients are still in the follow-up phase, and 5 patients were lost to follow-up. Complete cure was confirmed in 21 of the 25 patients who completed the study, and no adverse events were reported.

[0054] Conclusions: ActiGraft was found to be safe and effective in achieving complete closure of the sinus cavity after minimally invasive trephine pilonidal sinus surgery.

[0055] ActiGraft contains a fibrin scaffold that holds damaged tissue together and provides a temporary matrix and factors necessary for the natural healing process. The properties of ActiGraft position it as a promising treatment for pilonidal sinus.

[0056] Example 3 - Autologous blood clot promotes wound closure after stoma reversal Objective: Stoma reversal surgery can result in various complications, which can lead to longer hospital stays, significantly increased healthcare-related costs, and poor long-term outcomes. SSI remains the most common complication, ranging from 2% to 41%, so reducing the incidence of SSI after SR represents an important unmet need.

[0057] Autologous whole blood clots are generated from the patient's own peripheral blood at the point of care and have been suggested to form a protective scaffold that enhances the wound healing process, increasing cellular granulation formation and slowing bacterial infiltration into the wound.

[0058] Subjects: Four patients who underwent SR surgery and autologous whole blood clot treatment were studied. At the end of surgery, the wound was left partially open, and 18-24 hours after surgery, blood was taken from the patients, mixed with kaolin and calcium coagulants, and immediately injected into the open wound, allowing the blood to coagulate within the wound and form a clot. Patients were followed up for signs of infection and closure rates.

[0059] Results: Autologous clot therapy was applied in 4 patients after SR. Three weeks after autologous clot therapy, all patients showed no signs of infection and complete wound closure. Autologous clot therapy may accelerate the wound healing process and promote closure of SR wounds and the risk of infection.

Claims

1. One or more coagulants or anti-anticoagulants for use in a method for treating an abnormal cavitary space formed in a body part of a subject, comprising: The method further comprising: (i) drawing whole blood from the subject; (ii) mixing the subject's blood with the one or more coagulants or anti-anticoagulants; (iii) introducing the blood containing the clotting agent into the cavity space before the blood is completely coagulated; (iv) allowing the blood to clot within the abnormal cavitary space; The abnormal cavity space is a fistula-in-ano, a coagulant or an anti-anticoagulant.

2. A mixture comprising one or more coagulants or anti-anticoagulants and whole blood drawn from a subject, for use in treating an abnormal cavity space formed in a body part of a subject by introducing the composition into the abnormal cavity space before the blood has completely coagulated, causing the blood to coagulate within the abnormal cavity space, wherein the abnormal cavity space is a fistula-in-ano.

3. The mixture of claim 2 formed and used in the method of claim 1.

4. One or more coagulants or anti-anticoagulants described in claim 1, wherein (i) comprises the step of drawing whole blood from the subject and mixing it with an anticoagulant.

5. The one or more coagulants or anti-anticoagulants described in claim 3, wherein the anticoagulant is selected from the group consisting of ACD-A (anticoagulant citrate dextrose, solution A), EDTA (ethylenediaminetetraacetic acid), EGTA (ethylene glycol tetraacetic acid), citrate, heparin and oxalate.

6. One or more coagulants or anti-anticoagulants or mixtures described in any one of claims 1, 3 to 5, wherein the hollow space has two or more openings, and the method includes a step of sealing one or more openings of the hollow space to form a cavity.

7. One or more coagulants or anti-anticoagulants or mixtures described in any one of claims 1, 3 to 6, wherein (iv) comprises the step of applying a medical dressing or seal to the opening of the hollow space.

8. The one or more coagulants or anti-anticoagulants or mixtures described in claim 7, wherein said application occurs after a period of less than 10 minutes from said introduction.

9. One or more coagulants or anti-anticoagulants or mixtures according to any one of claims 1, 3 to 8, wherein the one or more coagulants are in liquid or powder form.

10. One or more coagulants or anti-anticoagulants or mixtures according to any one of claims 1, 3 to 9, wherein the one or more coagulants or anti-anticoagulants are selected from kaolin, Ca 2+ (e.g. in the form of a calcium salt such as calcium gluconate), Mg 2+ , negatively charged lipids (PL) and protamine sulfate.

11. The one or more coagulants or anti-anticoagulants or mixtures according to any one of claims 1, 3 to 10, wherein (ii) comprises the steps of first mixing the blood with calcium gluconate and then mixing the mixture of blood and calcium gluconate with kaolin.

12. The method of claim 1, further comprising the step of sealing the abnormal cavity space with a seal having an injection port prior to (iii), followed by (iii), wherein the introduction is via the injection port.

13. One or more coagulants or anti-anticoagulants or mixtures according to any one of claims 1, 3 to 12, wherein the hollow space comprises at least one opening formed in the exterior surface of the body.

14. The method of claim 1, wherein the abnormal cavity space includes two or more openings, and the method further comprises, prior to (iii), the step of: adjacent one of the openings to an expandable / contractable element in its contracted state and expanding it to seal the opening, thereby enabling the blood to be maintained within the cavity space when the blood is introduced into the cavity space through a non-sealed opening.

15. One or more coagulants or anti-anticoagulants or mixtures described in claim 14, further comprising the step of contracting the expandable / contractible element and retrieving the expandable / contractible element after the blood has sufficiently coagulated within the hollow space.

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