HEMOSTATIC DEVICE AND METHOD

Abstract

Use of a solid calcium compound in the fabrication of a hemostatic agent for reducing bleeding from a surgical site during and/or after a surgical treatment in a patient is provided, wherein the solid calcium compound is selected from the group consisting of calcium phosphate, calcium sulfate, calcium carbonate, calcium oxide, calcium hydroxide, hydroxyapatite, and a combination thereof.

Claims

1. Use of a solid calcium compound in the fabrication of a hemostatic agent for reducing bleeding from a surgical site during and/or after a surgical treatment in a patient, wherein the solid calcium compound is selected from the group consisting of calcium phosphate, calcium sulfate, calcium carbonate, calcium oxide, calcium hydroxide, hydroxyapatite, and a combination thereof.

2. The use of claim 1, wherein the hemostatic agent further comprises a phosphorus source, a sulfur source, or a phosphorus source and a sulfur source.

3. The use of claim 1, wherein the solid calcium compound has a porous structure with a porosity of about 30 vol % to about 90 vol %.

4. The use of claim 3, wherein the porosity is of about 60 vol % to about 80 vol %.

5. The use of claim 3, wherein the solid calcium compound is in a form of porous granules having a granular size of about 0.1 mm to about 2.5 mm.

6. The use of claim 5, wherein the granular size is of about 0.5 mm to about 1.5 mm.

7. The use of claim 3, wherein pores of the porous structure have a pore size in a range of about 30 μm to about 300 μm.

8. The use of claim 7, wherein the pores comprise interconnected pores.

9. The use of claim 1, wherein the surgical site comprises a bone cavity or a bone cut, and the bleeding is a bone bleeding, wherein the hemostatic agent is for contacting the bone cavity or the bone cut to reduce the bleeding.

10. The use of claim 9, wherein bone marrow is exposed by the bone cavity or the bone cut.

11. The use of claim 1, wherein the surgical treatment is a sternum closure treatment and the surgical site comprises a surgically-created sternum cavity.

12. The use of claim 1, wherein the solid calcium compound is calcium phosphate, calcium sulfate, hydroxyapatite or a mixture thereof.

13. The use of claim 1, wherein the solid calcium compound is a mixture of hydroxyapatite, calcium phosphate and calcium sulfate.

14. The use of claim 13, wherein the calcium phosphate is tetracalcium phosphate (TTCP), dicalcium phosphate, tricalcium phosphate, monocalcium phosphate or a mixture thereof; and the calcium sulfate is calcium sulfate hemihydrate (CSH), calcium sulfate dihydrate (CSD), anhydrous calcium sulfate, or a mixture thereof.

15. The use of claim 14, wherein the calcium phosphate is tetracalcium phosphate (TTCP), dicalcium phosphate, or a mixture thereof; and the calcium sulfate is calcium sulfate hemihydrate (CSH), calcium sulfate dihydrate (CSD), or a mixture thereof.

16. The use of claim 5, wherein pores of the porous structure have a pore size in a range of about 30 μm to about 300 μm.

17. The use of claim 16, wherein the pores comprise interconnected pores.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0026] The present invention includes (but not limited to) the following aspects:

[0027] 1. A hemostatic agent for reducing bleeding during and after a surgical treatment, wherein said hemostatic agent comprises a calcium source; wherein said hemostatic agent is in a porous form and has a porosity of about 40-90 vol %, preferably 60-80 vol %.

[0028] 2. The composition of said hemostatic agent in (1) contains at least 10 at % inorganic calcium ions.

[0029] 3. The calcium ions in (2) exist in an inorganic, biocompatible calcium compound comprising at least one selected from the group consisting of calcium phosphate, calcium sulfate, calcium carbonate, calcium oxide, and calcium hydroxide.

[0030] 4. The composition of said hemostatic agent in (2) further comprising a phosphorus source and/or a sulfur source.

[0031] 5. Said porous form in (1) is a porous granular form.

[0032] 6. The granules of said porous granular form in (5) have a size of about 0.1-2.5 mm and preferably about 0.5-1.5 mm.

[0033] 7. The pores of said granules in (6) have a pore size in the range of about 30 to 300 μm and preferably 50 to 250 μm, and are preferably interconnected.

[0034] 8. Said bleeding in (1) is a bone bleeding.

[0035] 9. Said bone in (8) is a sternum.

[0036] 10. A hemostatic treatment for sternum closure surgery comprising inserting a hemostatic agent into the bony cavity prior to closure of the surgically opened sternum; wherein said hemostatic agent is a synthetic, inorganic agent containing at least 10 at % inorganic calcium ions; wherein said calcium ions exist in any form of inorganic, biocompatible calcium compounds comprising at least one of the group consisting of calcium phosphate, calcium sulfate, calcium carbonate, calcium oxide, and calcium hydroxide; wherein said hemostatic agent is in a porous form and has a porosity of about 40-90 vol %, preferably 60-80 vol %.

[0037] Advantages of the present inventive hemostatic device and method for reducing bone bleeding during and post surgeries

[0038] (1) Unlike the existing organic and animal/human tissue-derived hemostatic devices which all have their aforementioned respective potential problems, the present inventive hemostatic agent is a 100% inorganic and entirely synthetic agent.

[0039] (2) The inventive device is designed to promote hemostasis during and post bone surgeries without potential organic and especially human or animal tissue-related safety risks. For this purpose, the composition of the present inventive device is designed to contain at least 10 at % inorganic calcium ions. The calcium ions in the product may exist in any form of inorganic, biocompatible calcium compounds such as calcium phosphate, calcium sulfate, calcium oxide, calcium hydroxide, etc.

[0040] (3) To enhance the hemostatic effect, the hemostatic agent may further comprise phosphorus and/or sulfur ions.

[0041] (4) For the purpose of minimally invasive delivery, the hemostatic agent is designed to have a granular form. The granules are designed to have a size of about 0.1-2.5 mm and preferably about 0.5-1.5 mm.

[0042] (5) In order to maximize the exposure of the hemostatic agent and at the same time to avoid the disintegration of the porous structure during delivery, the granules of the hemostatic agent are designed to have a highly porous form with a porosity level of about 40-90 vol % and preferably about 50-80 vol %.

[0043] (6) To assist blood to penetrate into the interior of each granule, the pores of the granules are designed to have a pore size substantially in the range of 30 to 300 μm, preferably 50 to 250 μm, and to be substantially interconnected.

[0044] To the knowledge of the present inventors, there have not been any prior art hemostatic device having all these characteristics.

Clinical Trials

[0045] Two complicated cases of open heart surgeries were completed using the hemostatic agent of the present invention in National Cheng Kung University Hospital, Tainan, Taiwan. The doctors used EZECHBONE® Granule to promote the union of median sternotomy of the patients. The doctors surprisingly found EZECHBONE® Granule also possesses good efficacy on hemostasis of bone marrow. 1st case was a 49 y/o female who was a CKD case receiving regular hemodialysis. Osteoporosis is one major problem of her. She underwent CABG*4 due to recent myocardial infarction. 0.24 g EZECHBONE® Granule was used. 2nd case was a 74 y/o old man who was noted huge aortic aneurysm (maximal diameter was 7.1 cm) extending from ascending aorta, aortic arch, and proximal descending aorta. Total ascending aorta and arch were replaced by prosthetic graft. Proximal descending aorta was implanted with cover stent graft, i.e. frozen elephant trunk stenting. Besides, right and left coronary arteries were bypassed with saphenous vein grafts. Innominate, left carotid and left subclavian arteries were also revascularized with prosthetic grafts. After operation, two cases recovered smoothly. Also, EZECHBONE® Granules showed wonderful hemostatic efficacy on them. For 1st case, 1st day after operation, only 80 c.c. blood was noted from drainage tubes (greatly less than the average amount of HD open heart patient: 200-300 c.c./day). Therefore, chest tubes were removed on the 2nd day after operation (also shorter than the average HD patients). For 2nd case, overall blood drainage was 170 c.c. (pericardial tubes 110 c.c. and left pleural chest tube: 60 c.c.). In this hospital, averaged POD-1 drainage amount≥800 c.c. The 2nd day: overall 170 c.c. but pleural chest tube: 50 c.c. So, left pleural chest tube was removed. The 3rd day: pericardial tubes 100 c.c. and the doctors separated them into 2 individual tubes. The 4th day: 1st tube 70 c.c. and the 2nd tube 20 c.c. So the 2nd tube was removed. The 5th day: 1st tube <70 c.c. and was removed. So, from these 2 cases experiences, the doctors found EZECHBONE® Granule not only promotes well bone union, but also possesses good effectiveness on hemostasis.

[0046] EZECHBONE® Granule is available from JOY MEDICAL DEVICES CORPORATION, 1F., No. 63, Luke 2nd Road, Luzhu District, Kaohsiung City, Taiwan. EZECHBONE® Granule has a particle size of about 0.4-1.2 mm, and a porosity of about 70-80 vol %, and is TTCP/DCPA/CSH-derived porous granules prepared based on the method disclosed in U.S. Pat. No. 8,784,551. The porous granules of calcium compound can be prepared from a mixed powers of TTCP/DCP/calcium sulfate (preferably TTCP/DCPA/CSH; more preferably TTCP/DCPA/CSH/CSD) and a pore forming agent, which is then mixed with a NH.sup.4+ solution to form a paste. The paste is hardened into a block in a mold, followed by washing the pore forming agent from the hardened block and breaking the block into porous granules; or breaking the block prior to washing. The porous granules are composed of hydroxyapatite, calcium sulfate (primarily CSD), and less significantly unreacted TTCP, DCP, and CSH. (DCPA: dicalcium phosphate anhydrous)

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