WO2015106119A1 - Radio-protector implants for protecting tissues from radiation side effects - Google Patents
Radio-protector implants for protecting tissues from radiation side effects Download PDFInfo
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- WO2015106119A1 WO2015106119A1 PCT/US2015/010844 US2015010844W WO2015106119A1 WO 2015106119 A1 WO2015106119 A1 WO 2015106119A1 US 2015010844 W US2015010844 W US 2015010844W WO 2015106119 A1 WO2015106119 A1 WO 2015106119A1
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- Prior art keywords
- depot implant
- tissue
- radio
- compound
- depot
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
Definitions
- the present invention relates to the field of pharmaceutical compositions, implants formed from pharmaceutical compositions, and methods of forming implants. More particularly, the present invention relates to delivering sustained release or depot delivery of radio- protector implants and methods for protecting tissues and glands from side effects of radiation treatment.
- Figures 1A and IB show examples of anatomic locations for delivery of sustained release or depot delivery of radio-protector implants
- Figure 2 details various particle design parameters useful in the present invention
- Figure 3 shows exemplary particle size ranges of hundreds by thousands of microns useful with the present invention.
- compositions and methods for preventing or minimizing side effects of radiation treatment include the direct injection of radio-protector compounds into tissue at, near, or that may be affected by radiation treatments.
- the radio-protector compounds are formulated into sustained release depot implants that can be directly injected into tissues to be protected.
- FIG. 1 shows example locations of various tissues to be protected.
- FIG. 1A shows the location of the thyroid gland and
- FIG. IB shows the location of various salivary glands including the parotid gland, sublingual gland, and submandibular gland that can be treated with the compositions and methods of the present invention.
- the depot implants are formed from a matrix of bio-degradable polymers, such as for example PLGA, PLA, PLLA, PEG, PMA, PMMA and the like, with the radio-protector compound contained within or on the depot implant.
- the depot implants become entrapped, stick, swell, or otherwise retain position within the tissue they are directly injected.
- the depot implants of the present invention release the radio-protector compound over a period longer than 24 hours. More preferably the depot implants of the present invention release the radio- protector compound over a period longer than 5 days. Yet more preferably the depot implants of the present invention release the radio-protector compound over a period longer than 2 weeks.
- the depot implants of the present invention can be fabricated using the PRINT micro / nano-particle technology (Liquidia Technologies, Inc).
- FIG. 2 provides examples of details of particle design parameters useful with the present invention including, but not limited to, particle modulus, porosity, size, shape, surface functionality, and chemical composition. Accordingly, the depot implants can be fabricated of virtually any size and/or shape from 50 nanometers in diameter to greater than 5000 micrometers in diameter.
- Depot implants can be manufactured utilizing PRINT® Technology previously described in, for example, US 8,263,129; US 8,128,393; US 7,976,759; WO 2008/118861; WO 2009/111588; US 2009-0165320; US 2007-0275193; US 2007-0264481; WO 2008/127455; US 2008-0181958; WO 2008/106503; and WO 2009/132206; each of which is incorporated herein by reference in its entirety.
- Radio protectors are compounds that are designed to reduce the damage in normal tissues caused by radiation. These compounds are often antioxidants and must be present before or at the time of radiation for effectiveness. Other agents, termed mitigators, may be used to minimize toxicity even after radiation has been delivered. Irradiation of noncancerous "normal" tissues during the course of therapeutic radiation can result in a range of side effects including self-limited acute toxicities, mild chronic symptoms, or severe organ dysfunction. The likelihood of developing these complications relates to the volume of an organ irradiated, the radiation dose delivered, fractionation of the delivered dose, the delivery of radiation modifiers, and individual radiosensitivity. Although improvements have been realized in radiation treatment, normal tissue toxicity remains a limiting factor in the treatment of many diseases with radiation therapy.
- normal tissue toxicity may be reduced by injecting or otherwise delivering the depot implants of the present invention to the normal tissue surrounding an area to be radiated.
- the radio protector agent protects normal tissues from a significant reduction in quality of life (i.e., mucositis, pneumonitis, myelopathy, xerostomia, proctitis, and leukencephalopathy).
- radio protector compounds useful with the present invention may include radical scavengers and antioxidants such as, for example, uperoxide dismutase (SOD), catalase, glutathione peroxidase, and glutathione reductase.
- radical scavengers and antioxidants such as, for example, uperoxide dismutase (SOD), catalase, glutathione peroxidase, and glutathione reductase.
- general antioxidant defense compounds are also useful, such as for example low molecular weight antioxidants, which are hydrogen atom-donating reducing agents such as ascorbic acid, tocopherols, polyphenols, and thiols such as glutathione.
- Further compounds useful with the present invention include almost any unsaturated organic molecule or molecule capable of H atom donation. Further compounds include, but are not limited to nitroxides, tempol, hormone and melatonin. Radiation mitigators can also be packaged in the depot implants of the present invention. Radiation mitigators can include, for example, cytokines and growth factors including, G-CSF and keratinocyte growth factor (KGF), palifermin, transforming growth factor (TGF)- . Further compounds useful with the present invention modulate cell cycle progression, such as for example cyclin dependent kinases (CDKs).
- CDKs cyclin dependent kinases
- Table 1 details product profile information for an exemplary radio-protector implant of the present invention.
- depot implants of the present invention may have a smallest dimension of between approximately 50 nm and approximately 7500 ⁇ .
- FIG. 3 shows exemplary particle size ranges of hundreds by thousands of microns.
- depot implant can have dimensions of (L X W X H): 80 nm x 80 nm x 320 nm; 200 nm x 200 nm x 600 nm; 1 ⁇ m x 1 ⁇ m x 1 ⁇ ; 3 ⁇ x 3 ⁇ x6 ⁇ ; 20 ⁇ x 20 ⁇ m x 20 ⁇ ; 25 ⁇ X 25 ⁇ X 50 ⁇ m ; 225 ⁇ X 225 ⁇ X 2,925 ⁇ ; 150 ⁇ X 150 ⁇ X 1,500 ⁇ m ; or 180 ⁇ X 160 ⁇ m X 3,000 ⁇ m .
- the implants are delivered by direct injection into the salivary glands, thyroid, tongue, throat, or other tissue desired to be protected.
- the implants are injected in a dry state, saline, delivery formulation, a suspension of implants, or the like.
- Depot implants of the present invention can have loading of the radio-protector compound from between 1 wt% to 99 wt% of the overall depot implant weight.
- the radio-protector compound can be loaded into the depot implant between 10 wt% to 90 wt% of the overall depot implant weight.
- the radio-protector compound can be loaded into the depot implant between 20 wt% to 80 wt% of the overall depot implant weight.
- the radio-protector compound can be loaded into the depot implant between 30 wt% to 70 wt% of the overall depot implant weight. In other embodiments, the radio-protector compound can be loaded into the depot implant between 40 wt% to 60 wt% of the overall depot implant weight. In other embodiments, the radio-protector compound can be loaded into the depot implant between 1 wt% to 10 wt% of the overall depot implant weight. In other embodiments, the radio-protector compound can be loaded into the depot implant between 1 wt% to 7 wt% of the overall depot implant weight.
- the depot implants can include further compounds that treat or sooth the effected tissue, such as for example anti inflammatory agents, anti infective agents, pain reducing agents, pH balancing agents, natural or synthetic agents, anti-cancer agents, immunomodulators, combinations thereof, and the like.
- the implants of the present invention can include compounds such as, for example, small molecule drugs, biologic molecules, anti-infective agents, immunomodulators, antiinflammatory agents, proteins, protein fragments, antibodies, antibody fragments, nucleic acids, DNA, siRNA, RNA, or the like.
- the implants of the present invention can be used to treat dry mouth, periodontitis, oral mucositis, or the like and can be directly injected into the salivary glands, thyroid, tongue, throat, or the like.
- the depot implant is 100% bioresorbable leaving no residual materials following degradation.
Abstract
The disclosure relates to the field of pharmaceutical compositions, implants formed from pharmaceutical compositions, and methods of forming implants. More particularly, the present invention relates to delivering sustained release or depot delivery of radio-protector implants and methods for protecting tissues and glands from side effects of radiation treatment.
Description
IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
PATENT APPLICATION
RADIO-PROTECTOR IMPLANTS FOR PROTECTING TISSUES FROM RADIATION
SIDE EFFECTS
CROSS REFERENCE TO RELATED APPLICATIONS
[001] The present Application is a PCT International Application claiming priority to U.S. Provisional Application No. 61/926,531, filed on January 13, 2014, the entire contents of which are hereby incorporated by reference for all purposes.
FIELD OF THE DISCLOSURE
[002] The present invention relates to the field of pharmaceutical compositions, implants formed from pharmaceutical compositions, and methods of forming implants. More particularly, the present invention relates to delivering sustained release or depot delivery of radio- protector implants and methods for protecting tissues and glands from side effects of radiation treatment.
BACKGROUND OF THE FIELD OF THE INVENTION
[003] As the incidence of cancer and other ailments rise, side effects from treatments for such diseases and conditions continue to rise. Some side effects include dry mouth and oral mucositis driven by increasing cancer treatments. In the US alone in 2013 it is estimated that there are 53,000 new head and neck cancer patients and 60,000 new thyroid cancer patients. As typical treatment for such cancers, and other cancers, include radiation treatment of the affected area there are resulting side effects of the radiation. One drawback of the current treatment landscape is the lack of effective protective mechanisms for reducing unwanted damage to otherwise healthy tissues during radiation treatment. The present invention provides a radio- protector implant and methods of protecting tissues during radiation treatments.
BRIEF DESCRIPTION OF THE FIGURES
Figures 1A and IB show examples of anatomic locations for delivery of sustained release or depot delivery of radio-protector implants;
Figure 2 details various particle design parameters useful in the present invention; and Figure 3 shows exemplary particle size ranges of hundreds by thousands of microns useful with the present invention.
DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION
[004] Provided herein are pharmaceutical compositions and methods for preventing or minimizing side effects of radiation treatment. Such methods include the direct injection of radio-protector compounds into tissue at, near, or that may be affected by radiation treatments. In other aspects of the present invention the radio-protector compounds are formulated into sustained release depot implants that can be directly injected into tissues to be protected. FIG. 1 shows example locations of various tissues to be protected. FIG. 1A shows the location of the thyroid gland and FIG. IB shows the location of various salivary glands including the parotid gland, sublingual gland, and submandibular gland that can be treated with the compositions and methods of the present invention. In some embodiments, the depot implants are formed from a matrix of bio-degradable polymers, such as for example PLGA, PLA, PLLA, PEG, PMA, PMMA and the like, with the radio-protector compound contained within or on the depot implant. In preferred embodiments, the depot implants become entrapped, stick, swell, or otherwise retain position within the tissue they are directly injected. Preferably the depot implants of the present invention release the radio-protector compound over a period longer than 24 hours. More preferably the depot implants of the present invention release the radio- protector compound over a period longer than 5 days. Yet more preferably the depot implants of the present invention release the radio-protector compound over a period longer than 2 weeks.
[005] As will be appreciated by one of ordinary skill in the art, the depot implants of the present invention can be fabricated using the PRINT micro / nano-particle technology (Liquidia Technologies, Inc). FIG. 2 provides examples of details of particle design parameters useful with the present invention including, but not limited to, particle modulus, porosity, size, shape, surface functionality, and chemical composition.
Accordingly, the depot implants can be fabricated of virtually any size and/or shape from 50 nanometers in diameter to greater than 5000 micrometers in diameter. Depot implants can be manufactured utilizing PRINT® Technology previously described in, for example, US 8,263,129; US 8,128,393; US 7,976,759; WO 2008/118861; WO 2009/111588; US 2009-0165320; US 2007-0275193; US 2007-0264481; WO 2008/127455; US 2008-0181958; WO 2008/106503; and WO 2009/132206; each of which is incorporated herein by reference in its entirety.
[006] Radio protectors are compounds that are designed to reduce the damage in normal tissues caused by radiation. These compounds are often antioxidants and must be present before or at the time of radiation for effectiveness. Other agents, termed mitigators, may be used to minimize toxicity even after radiation has been delivered. Irradiation of noncancerous "normal" tissues during the course of therapeutic radiation can result in a range of side effects including self-limited acute toxicities, mild chronic symptoms, or severe organ dysfunction. The likelihood of developing these complications relates to the volume of an organ irradiated, the radiation dose delivered, fractionation of the delivered dose, the delivery of radiation modifiers, and individual radiosensitivity. Although improvements have been realized in radiation treatment, normal tissue toxicity remains a limiting factor in the treatment of many diseases with radiation therapy. Based on the intimate relationship between tumors and their normal host tissues and surrounding critical structures and the need to irradiate clinically uninvolved normal tissue margins that are potentially contaminated with microscopic disease, normal tissue toxicity may be reduced by injecting or otherwise delivering the depot implants of the present invention to the normal tissue surrounding an area to be radiated. The radio protector agent protects normal tissues from a significant reduction in quality of life (i.e., mucositis, pneumonitis, myelopathy, xerostomia, proctitis, and leukencephalopathy).
[007] A number of compounds have been described that meet most or all of the criteria in preclinical studies or in early clinical trials for radio protection, however, only amifostine is currently in clinical use. Further suitable radio protector compounds useful with the present invention may include radical scavengers and antioxidants such as, for example, uperoxide dismutase (SOD), catalase, glutathione peroxidase, and glutathione reductase. Moreover, general antioxidant defense compounds are also useful, such as
for example low molecular weight antioxidants, which are hydrogen atom-donating reducing agents such as ascorbic acid, tocopherols, polyphenols, and thiols such as glutathione. Further compounds useful with the present invention include almost any unsaturated organic molecule or molecule capable of H atom donation. Further compounds include, but are not limited to nitroxides, tempol, hormone and melatonin. Radiation mitigators can also be packaged in the depot implants of the present invention. Radiation mitigators can include, for example, cytokines and growth factors including, G-CSF and keratinocyte growth factor (KGF), palifermin, transforming growth factor (TGF)- . Further compounds useful with the present invention modulate cell cycle progression, such as for example cyclin dependent kinases (CDKs).
[008] Table 1 details product profile information for an exemplary radio-protector implant of the present invention.
[009] Table 1: Radio-protector Implant Profile
Further example of depot implants of the present invention may have a smallest dimension of between approximately 50 nm and approximately 7500 μιη. FIG. 3 shows exemplary particle size ranges of hundreds by thousands of microns. In embodiments of the present invention, depot implant can have dimensions of (L X W X H): 80 nm x 80 nm x 320 nm; 200 nm x 200 nm x 600 nm; 1 μm x 1 μm x 1 μιη; 3 μιη x 3 μιη x6 μιη; 20 μιη x 20 μm x 20 μιη; 25 μιη X 25 μιη X 50 μm ; 225 μιη X 225 μιη X 2,925 μιη; 150 μιη X 150 μιη X 1,500 μm ; or 180 μιη X 160 μm X 3,000 μm . FIG. 3 In some embodiments, the implants are delivered by direct injection into the salivary glands, thyroid, tongue, throat, or other tissue desired to be protected. In alternative embodiments the implants are injected in a dry state, saline, delivery formulation, a suspension of implants, or the like.
[0010] Depot implants of the present invention can have loading of the radio-protector compound from between 1 wt% to 99 wt% of the overall depot implant weight. In other embodiments, the radio-protector compound can be loaded into the depot implant between 10 wt% to 90 wt% of the overall depot implant weight. In other embodiments, the radio-protector compound can be loaded into the depot implant between 20 wt% to 80 wt% of the overall depot implant weight. In other embodiments, the radio-protector compound can be loaded into the depot implant between 30 wt% to 70 wt% of the overall depot implant weight. In other embodiments, the radio-protector compound can be loaded into the depot implant between 40 wt% to 60 wt% of the overall depot implant weight. In other embodiments, the radio-protector compound can be loaded into the depot implant between 1 wt% to 10 wt% of the overall depot implant weight. In other embodiments, the radio-protector compound can be loaded into the depot implant between 1 wt% to 7 wt% of the overall depot implant weight.
[0011] In some embodiments, the depot implants can include further compounds that treat or sooth the effected tissue, such as for example anti inflammatory agents, anti infective agents, pain reducing agents, pH balancing agents, natural or synthetic agents, anti-cancer agents, immunomodulators, combinations thereof, and the like. The implants of the present invention can include compounds such as, for example, small molecule drugs, biologic molecules, anti-infective agents, immunomodulators, antiinflammatory agents, proteins, protein fragments, antibodies, antibody fragments, nucleic acids, DNA, siRNA, RNA, or the like. The implants of the present invention can be used to treat dry mouth, periodontitis, oral mucositis, or the like and can be directly injected into the salivary glands, thyroid, tongue, throat, or the like.
[0012] Preferably, the depot implant is 100% bioresorbable leaving no residual materials following degradation.
Claims
1. A method of reducing unwanted side effects of radiation treatments, comprising: delivering directly into a tissue to be affected by radiation a depot implant, wherein the depot implant comprises a bio degradable polymer matrix and a radio protector compound; and
allowing the bio degradable polymer of the depot implant to degrade in the tissue thereby releasing the radio protector compound to protect the tissue from subsequent radiation treatment.
2. The method of claim 1, wherein the depot implant releases the radio protector compound for more than 24 hours.
3. The method of claim 1, wherein the depot implant releases the radio protector compound for more than 5 days.
4. The method of claim 1, wherein the depot implant releases the radio protector compound for more than 2 weeks.
5. The method of claim 1, wherein the radio protector compound is amifostine.
6. The method of claim 1, wherein the tissue is a gland, a salivary gland, thyroid, lymph node, or muscle.
7. The method of claim 1, wherein the bio degradable polymer matrix comprises at least one of PLGA, PLA, PLLA, PEG, PMA, and PMMA.
8. A method for protecting tissue from unwanted side effects of radiation treatment, comprising: direct injection into a tissue to be protected of a depot implant comprising a radio protector compound.
9. The method of claim 8, wherein the radio protector compound is amifostine and the depot implant comprises PLGA.
10. The method of claim 9, wherein the depot implant releases amifostine for more than 24 hours.
11. The method of claim 9, wherein the depot implant releases amifostine for more than 5 days.
12. The method of claim 9, wherein the depot implant releases amifostine for more than 2 weeks.
13. The method of claim 9, wherein the tissue is a gland, a salivary gland, thyroid, lymph node, or muscle.
14. A method of protecting or treating tissue from side effects of a medical procedure, comprising:
delivering directly into a tissue to be affected by a medical procedure a depot implant, wherein the depot implant comprises a bio degradable polymer matrix and an active pharmaceutical or therapeutic compound; and
allowing the bio degradable polymer of the depot implant to degrade in the tissue thereby releasing the compound to protect or treat the tissue from the medical procedure.
15. The method of claim 14, wherein the depot implant releases the pharmaceutical or therapeutic compound for more than 24 hours.
16. The method of claim 14, wherein the depot implant releases the pharmaceutical or therapeutic compound for more than 5 days.
17. The method of claim 14, wherein the depot implant releases the pharmaceutical or therapeutic compound for more than 2 weeks.
18. The method of claim 14, wherein the tissue is a gland, a salivary gland, thyroid, lymph node, or muscle.
19. The method of claim 14, wherein the pharmaceutical or therapeutic compound is amifostine.
20. The method of claim 14, wherein the bio degradable polymer matrix comprises at least one of PLGA, PLA, PLLA, PEG, PMA, and PMMA.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US201461926531P | 2014-01-13 | 2014-01-13 | |
US61/926,531 | 2014-01-13 |
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WO2015106119A1 true WO2015106119A1 (en) | 2015-07-16 |
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006091187A1 (en) * | 2005-02-22 | 2006-08-31 | Landauer Michael R | Isoflavonoids for preventing radiation- and chemotherapy- induced weight loss |
US20120164207A1 (en) * | 2010-12-23 | 2012-06-28 | Gooberman Lance L | Degradable networks for sustained release and controlled release depot drug delivery applications |
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2015
- 2015-01-09 WO PCT/US2015/010844 patent/WO2015106119A1/en active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006091187A1 (en) * | 2005-02-22 | 2006-08-31 | Landauer Michael R | Isoflavonoids for preventing radiation- and chemotherapy- induced weight loss |
US20120164207A1 (en) * | 2010-12-23 | 2012-06-28 | Gooberman Lance L | Degradable networks for sustained release and controlled release depot drug delivery applications |
Non-Patent Citations (1)
Title |
---|
SRINIVASAN ET AL.: "Radioprotection, pharmacokinetic and behavioural studies in mouse implanted with biodegradable drug (amifostine) pellets.", INT. J. RADIAL. BIOL, vol. 78, no. 6, 2002, pages 535 - 543, Retrieved from the Internet <URL:http://xa.yimg.com/kq/groups/22812288/1341180002/name/Srinivasan+-+Amifostine.pdf> [retrieved on 20150314] * |
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