Cavity-filling biopsy site markers

• US 9,649,093 B2
• Filed: 01/14/2016
• Issued: 05/16/2017
• Est. Priority Date: 02/02/1999
• Status: Expired due to Fees

• Current Assignee: Senorx Incorporated (Becton, Dickinson & Co)
• Original Assignee: Senorx Incorporated (Becton, Dickinson & Co)
• Inventors: Jones, Michael L., Burbank, Fred H., Lubock, Paul
• Primary Examiner(s): PELHAM, JOSEPH MOORE
• Application Number:
  US14/995,667
• Publication Number:
  US 20160120510A1
• Time in Patent Office: 488 Days
• CPC Class Codes: A61B 10/02 Instruments for taking cell samples or for biopsy A61B10/0038 and A61B10/0045 take precedence; needle locating or guiding means A61B17/3403; samplers for enzymology or microbiology C12M1/26; sampling or preparing biological specimens G01N33/48
• CPC Class Codes: A61B 2017/00004 (bio)absorbable, (bio)resorbable or resorptive
• CPC Class Codes: A61B 2090/3908 Soft tissue, e.g. breast tissue
• CPC Class Codes: A61B 2090/392 Radioactive markers
• CPC Class Codes: A61B 2090/3925 ultrasonic
• CPC Class Codes: A61B 2090/395 with marking agent for marking skin or other tissue
• CPC Class Codes: A61B 2090/3954 magnetic, e.g. NMR or MRI
• CPC Class Codes: A61B 2090/3966 Radiopaque markers visible in an X-ray image
• CPC Class Codes: A61B 2090/3987 Applicators for implanting markers
• CPC Class Codes: A61B 2090/3995 Multi-modality markers
• CPC Class Codes: A61B 6/12 Arrangements for detecting or locating foreign bodies
• CPC Class Codes: A61B 8/0833 involving detecting or locating foreign bodies or organic structures
• CPC Class Codes: A61B 8/481 involving the use of contrast agent, e.g. microbubbles introduced into the bloodstream analysis of echo signal exploiting properties of a contrast enhancer in devices for short-range imaging with acoustic waves G01S7/52039
• CPC Class Codes: A61B 90/39 Markers, e.g. radio-opaque or breast lesions markers
• CPC Class Codes: A61K 49/006 Biological staining of tissues in vivo, e.g. methylene blue or toluidine blue O administered in the buccal area to detect epithelial cancer cells, dyes used for delineating tissues during surgery
• CPC Class Codes: A61K 49/222 characterised by a special physical form, e.g. emulsions, liposomes
• CPC Class Codes: A61M 37/0069 Devices for implanting pellets, e.g. markers or solid medicaments for introducing of radioactive sources for interstitial radiation therapy, i.e. brachytherapy A61N5/1027

Abstract

A mass includes particles that exhibit an in vivo lifetime and that include a bioresorbable material and bubble cavities disposed in the particles, wherein the bubble cavities have length, width, and height dimensions at least one of which is less than or equal to about 2000 microns. The mass exhibits enhanced detectability by ultrasound energy during the lifetime; the lifetime begins upon exposure to in vivo fluids and ends between about 2 and about 20 weeks afterward; and a zero or non-zero fluid-to-solid ratio.

Claims

1. A mass comprising:

particles that exhibit an in vivo lifetime and that include a bioresorbable material

and

bubble cavities disposed in the particles,

wherein

the bubble cavities have length, width, and height dimensions at least one of which is less than or equal to about 2000 microns;

the mass exhibits enhanced detectability by ultrasound energy during the lifetime;

and

the lifetime begins upon exposure to in vivo fluids and ends between about 2 and about 20 weeks afterward.

2. The mass of claim 1 wherein the lifetime ends between about 6 and about 12 weeks afterward.

3. The mass of claim 2 wherein all of the length, width, and height dimensions are less than or equal to about 2000 microns.

4. The mass of claim 3 wherein all of the length, width, and height dimensions are between about 10 and about 500 microns.

5. The mass of claim 4 wherein all of the length, width, and height dimensions are between about 20 and about 200 microns.

6. The mass of claim 3 having a volume between about 0.2 and about 1.2 ml.

7. The mass of claim 6 having a volume of about 0.5 ml.

8. The mass of claim 6 wherein the bioresorbable material comprises a bioresorbable polymeric material.

9. The mass of claim 8 wherein the bioresorbable polymeric material comprises polymers, copolymers, polymer alloys, polymer mixtures, or other combinations of poly(esters), poly(hydroxy acids), poly(lactones), poly(amides), poly(ester-amides), poly(amino acids), poly(anhydrides), poly(orthoesters), poly(carbonates), poly(phosphazines), poly(thioesters), poly(urethanes), poly(ester urethanes), polysaccharides, polylactic acids, polyglycolic acids, polycaproic acids, polybutyric acids, or polyvaleric acids.

10. The mass of claim 9 wherein the bioresorbable polymeric material:

comprises polymers, copolymers, polymer alloys, polymer mixtures, or other combinations of polyglycolic acids, polylactic acids, and polycaproic acids

and

has an average molecular weight of less than about 60 kD.

11. The mass of claim 10 wherein the bioresorbable material comprises about 65% by weight polylactic acid and about 35% by weight polyglycolic acid.

12. The mass of claim 8 further comprising less than or equal to 10% by weight of a blowing agent.

13. The mass of claim 12 further comprising less than or equal to 5% by weight of a blowing agent.

14. The mass of claim 13 further comprising less than or equal to 2% by weight of a blowing agent.

15. The mass of claim 14 wherein the blowing agent comprises any one or any combination of sodium bicarbonate, ammonium carbonate, sodium boron hydride, silicon oxy-hydride, hydrochlorofluorocarbon compounds, chlorofluorocarbon compounds, mixtures of sodium bicarbonate, ammonium carbonate, sodium boron hydride, silicon oxy-hydride, hydrochlorofluorocarbon compounds, and chlorofluorocarbon compounds, hexane, heptane, heptene, propyl alcohol, or isopropyl alcohol.

16. The mass of claim 15 wherein the blowing agent comprises sodium bicarbonate.

17. The mass of claim 12 further comprising a binding agent.

18. The mass of claim 17 wherein the binding agent comprises gelatin, polyethylene glycol, polyvinyl alcohol, glycerin, acrylic hydrogels, organic hydrogels, or their combinations.

19. The mass of claim 17 comprises gelatin in a weight proportion of about 1 part gelatin to between about 2 parts polymeric material to about 5 parts polymeric material.

20. The mass of claim 19 wherein the weight proportion of about 1 part gelatin to between about 1 part polymeric material to about 3 parts polymeric material.

21. The mass of claim 20 wherein gelatin comprises bovine collagen, porcine collagen, ovine collagen, equine collagen, synthetic collagen, agar, synthetic gelatin, or their combinations.

22. The mass of claim 19 further comprising a magnetic resonance imaging (MRI) agent, a colorant, a radioactive material, or a radiopaque material.

23. The mass of claim 22 comprising a radiopaque marker formed in a recognizable shape not naturally found within a patient'"'"'s body.

24. The mass of claim 22 further comprising a biocompatible liquid.

25. The mass of claim 24 wherein the biocompatible liquid comprises any one or any combination of sterile saline, sterile saline containing an pharmaceutical agent, sterile saline containing an anesthetic agent, sterile saline containing a hemostatic agent, sterile saline containing a colorant, sterile saline containing a radio contrast agent, sterile saline containing an osmotic agent, sterile sugar solution, sterile sugar solution containing a pharmaceutical agent, sterile sugar solution containing an anesthetic agent, sterile sugar solution containing a hemostatic agent, sterile sugar solution containing a colorant, sterile sugar solution containing a radio contrast agent, biocompatible oils, biocompatible oils containing an pharmaceutical agent, biocompatible oils containing an anesthetic agent, biocompatible oils containing a hemostatic agent, biocompatible oils containing a colorant, biocompatible oils containing a radio contrast agent, adrenochrome, algin, alginic acid, aminocaproic acid, batroxobin, carbazochrome salicylate, cephalins, cotarmine, ellagic acid, epinephrine, ethamsylate, factor VIII, factor IX, factor XIII, fibrin, fibrinogen, naphthoquinone, oxamarin, oxidized cellulose, styptic collodion, sulamrin, thrombin, thromboplastin (factor III), tolonium chloride, tranexamic acid, or vasopression.

26. The mass of claim 25 wherein said biocompatible liquid comprises a pharmaceutical agent selected from the group consisting of penicillins, cephalosporins, vancomycins, aminoglycosides, quinolones, polymyxins, erythromycins, tetracyclines, streptomycins, sulfa drugs, chloramphenicols, clindamycins, lincomycins, sulfonamides, paclitaxel, docetaxel, acetyl sulfisoxazole, alkylating agents, antimetabolites, plant alkaloids, mechlorethamine, chlorambucil, cyclophosphamide, melphalan, ifosfamide, methotrexate, 6-mercaptopurine, 5-fluorouracil, cytarabine, vinblastine, vincristine, etoposide, doxorubicin, daunomycin, bleomycin, mitomycin, carmustine, lomustine, cisplatin, interferon, asparaginase, tamoxifen, flutamide, amantadines, rimantadines, ribavirins, idoxuridines, vidarabines, trifluridines, acyclovirs, ganciclovirs, zidovudines, foscarnets, interferons, prochlorperzine edisylate, ferrous sulfate, aminocaproic acid, mecamylamine hydrochloride, procainamide hydrochloride, isoproterenol sulfate, phenmetrazine hydrochloride, bethanechol chloride, methacholine chloride, isopropamide iodide, tridihexethyl chloride, phenformin hydrochloride, methylphenidate hydrochloride, theophylline cholinate, cephalexin hydrochloride, diphenidol, meclizine hydrochloride, prochlorperazine maleate, phenoxybenzamine, thiethylperzine maleate, anisindone, diphenadione erythrityl tetranitrate, isoflurophate, acetazolamide, methazolamide, bendroflumethiazide, chloropromaide, tolazamide, chlormadinone acetate, phenaglycodol, allopurinol, aluminum aspirin, hydrocortisone, hydrocorticosterone acetate, cortisone acetate, dexamethasone and its derivatives such as betamethasone, triamcinolone, methyltestosterone, 17-S-estradiol, ethinyl estradiol, ethinyl estradiol 3-methyl ether, prednisolone, 17-hydroxyprogesterone acetate compounds, 19-nor-progesterone, norgestrel, norethindrone, norethisterone, norethiederone, progesterone, norgesterone, norethynodrel, aspirin, indomethacin, naproxen, fenoprofen, sulindac, indoprofen, nitroglycerin, isosorbide dinitrate, propranolol, timolol, atenolol, alprenolol, cimetidine, clonidine, imipramine, dihydroxyphenylalanine, theophylline, calcium gluconate, ketoprofen, ibuprofen, cephalexin, haloperidol, zomepirac, ferrous lactate, vincamine, diazepam, phenoxybenzamine, milrinone, capropril, mandol, quanbenz, hydrochlorothiazide, ranitidine, flurbiprofen, fenufen, fluprofen, tolmetin, alclofenac, mefenamic, flufenamic, difuinal, nizatidine, sucralfate, etintidine, tetratolol, minoxidil, chlordiazepoxide, diazepam, amitriptyline, imipramine, prostaglandins, coagulation factors, adrenochrome, algin, alginic acid, aminocaproic acid, batroxobin, carbazochrome salicylate, cephalins, cotarmine, ellagic acid, epinephrine, ethamsylate, factor VIII, factor IX, factor XIII, fibrin, fibrinogen, naphthoquinone, oxamarin, oxidized cellulose, styptic collodion, sulamrin, thrombin, thromboplastin (factor III), tolonium chloride, tranexamic acid, or vasopression or analogs of these compounds, derivatives of these compounds, or pharmaceutically acceptable salts of these compounds, analogs, or derivatives.

27. The mass of claim 24 wherein said bio-resorbable material is effective to form a gel upon introduction within the body of an animal.