Formulations and compositions of vitamin D analogs for treating and preventing cancer and other diseases
Inventors
Assignees
Publication Number
US-10258635-B2
Publication Date
2019-04-16
Expiration Date
2034-07-12
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Abstract
This invention is for formulations of analogs of the non-toxic and inert Vitamin D3, its non-toxic and mostly inert pre-hormone and its toxic and biologically active hormone, and for using these formulations for preventing and treating certain cancers such as breast, prostate, ovarian, kidney, renal and other cancers, Vitamin D deficiency, autoimmune disease such as Multiple Sclerosis, hypertension, osteoporosis, bone diseases, rickets, psoriasis and infectious diseases. This invention also discloses compositions of the analogs of the non-toxic and inert Vitamin D3 and the non-toxic and mostly inert Vitamin D3 pre-hormone.
Core Innovation
Embodiments of the present invention are directed to new compositions and formulations of Vitamin D analogs, specifically derivatives of non-toxic and inert Vitamin D3, its pre-hormone, and its biologically active hormone. These analogs, such as AMPI-109, AMPI-105, AMPI-106, and AMPI-107, are designed to bind tightly into the Vitamin D receptor (VDR) and can be used therapeutically at lower, less toxic doses than their Vitamin D counterparts.
The invention addresses the limitations of current Vitamin D-based therapies, particularly the toxicity associated with pharmacological doses of active Vitamin D hormone, such as hypercalcemia and significant body weight loss. Further, the rapid catabolic degradation of active Vitamin D by CYP-hydroxylases requires high dosages, which amplifies toxicity. The analogs proposed in this invention are formulated to overcome these issues by covalently attaching to VDR, thereby reducing catabolism and systemic toxicity while prolonging therapeutic exposure.
A key advancement is the nanoencapsulation of these Vitamin D analogs within the lipid bilayer of phospholipid nanosomes using supercritical, critical, or near-critical fluids. This nanoencapsulation increases serum stability, prolongs the circulation time of the analogs, protects against premature hydrolysis, and further decreases systemic toxicity, allowing for enhanced therapeutic activity and improved indices of safety and efficacy.
Claims Coverage
There are two independent claims describing two inventive features for treating prostate or kidney cancer using specific formulations of Vitamin D3 analogs.
Nanosomes containing Vitamin D3-3-bromoacetate or Vitamin D3-3-epoxide for treating prostate or kidney cancer
A method of treating a disease responsive to Vitamin D3 or its analog, specifically prostate cancer or kidney cancer, by providing a medicament comprising a plurality of nanosomes. These nanosomes have at least one bilayer of phospholipid in which Vitamin D3-3-bromoacetate (D3-3-BE) or Vitamin D3-3-epoxide (D3-3-EPO) is distributed. The method includes administering an effective amount of this medicament to treat the disease.
Gel capsule with oil base containing Vitamin D3-3-bromoacetate or Vitamin D3-3-epoxide for treating prostate or kidney cancer
A method of treating a disease responsive to Vitamin D3 or its analog, specifically prostate cancer or kidney cancer, by providing a gel capsule. The capsule consists of a gelatin outer layer defining an inner volume, which contains an oil base in which either Vitamin D3-3-bromoacetate (D3-3-BE) or Vitamin D3-3-epoxide (D3-3-EPO) is dissolved. The method includes administering an effective amount of D3-3-BE or D3-3-EPO by ingesting one or more gel capsules.
The inventive features claim two different pharmaceutical formulations for administering Vitamin D3-3-bromoacetate or Vitamin D3-3-epoxide: nanosomal bilayer phospholipid vesicles and gelatin capsules with oil base, both intended for effective treatment of prostate or kidney cancer.
Stated Advantages
The formulations prolong circulation time and reduce systemic toxicity of Vitamin D analogs while enhancing therapeutic index.
Nanoencapsulation protects the ester bond of Vitamin D analogs from hydrolysis, increasing their half-life.
Encapsulation allows the analogs to kinetically engage the Vitamin D receptor, increasing potency with less toxicity.
The analogs can be used at lower doses than their Vitamin D counterparts and are less toxic.
The nanoencapsulated analogs increase serum stability.
The invention demonstrates strong anti-tumor activity without significant toxicity, as evidenced by stable body-weights in treated animal models.
Documented Applications
Prevention and treatment of prostate, breast, ovarian, kidney, and renal cancers.
Treatment of Vitamin D deficiency.
Management of autoimmune diseases such as Multiple Sclerosis.
Treatment of hypertension.
Treatment of osteoporosis and other bone diseases.
Treatment of rickets.
Treatment of psoriasis.
Treatment of infectious diseases.
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