WO2020172262A1

WO2020172262A1 - Chromium composition and methods thereof

Info

Publication number: WO2020172262A1
Application number: PCT/US2020/018810
Authority: WO
Inventors: Janine JAMES
Original assignee: James Janine
Priority date: 2019-02-19
Filing date: 2020-02-19
Publication date: 2020-08-27

Abstract

The present invention relates to a composition including chromium (Cr) for use in the treatment of debilitating neural diseases such as multiple sclerosis (MS) by administering a composition including chromium in an effective amount to a subject in need thereof. The present invention also relates to a kit comprising the chromium composition.

Description

CHROMIUM COMPOSITION AND METHODS THEREOF

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims the benefit of priority to U.S. Provisional Patent Application No. 62/807,335 filed February 19, 2019.

TECHNICAL FIELD

[0002] Embodiments generally relate to a composition including chromium (Cr) for use as a medicament. More particularly, embodiments relate to a composition including Cr for use in the treatment of debilitating neural diseases such as multiple sclerosis (MS).

BACKGROUND

[0003] Generally, a neuron has a resting potential of about -70 mV from a relatively high concentration of Potassium (K⁺) ions in the cell and a relatively high concentration of Sodium (Na⁺) ions in the extracellular space. A protective layer of cells, called the myelin sheath, wrap around a nerve axon in a spiral fashion to insulate the neuron. Periodic interruptions in the myelin sheath leave portions of the axon uncovered. These uncovered portions are called the nodes of Ranvier, and include Na⁺ channels that are excited for impulse propogation in myelinated fibers during saltatory conduction. In unmyelinated fibers, however, an entire axonal membrane is involved in impulse propagation as local circuits depolarize the adjacent piece of the axonal membrane in a continuous, sequential fashion to allow Na⁺ flux into the nerve that is much greater than in myelinated fibers. The structure and function of the myelin sheath is well characterized (Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th Ed., Chapter 4). Neural impulses that are not properly transmitted cause the brain to improperly interpret“noisy” signals as numbness, tingling, and/or pain when the myelin sheath is damaged. This effect occurs in debilitating diseases such as MS. Thus, there is considerable room for improvement to provide a medicament for use in debilitating neural diseases such as MS.

DFTATLFD DESCRIPTION

[0004] Embodiments may involve a composition including Cr for use as a medicament, a composition including Cr for use in the treatment of debilitating neural diseases such as MS, and so on. In one example, altering the ionic composition of the cerebrospinal fluid (CSF) by the addition of Cr might decrease the symptoms associated with MS by allowing the impulse propagation of an exposed neuron to continue to flow. For example, a commercially available Chromic Chloride Injection (e.g., about 4 mcg/ml) conventionally used as a supplement in Total Parenteral Nutrition (TPNs) may be administered to a subject in need thereof to treat MS according to embodiments. In one example MS treatment may include the minimization of improper impulse propagation, observed in unmyelinated fibers, and associated symptoms. In a further example, Cr (e.g., from a Chromic Chloride injection) may be used to treat the symptoms of a spinal chord injury, such as extreme back pain or pressure (e.g., in the neck, head, back, etc.) weakness, incoordination or paralysis in any part of the body, numbness, tingling or loss of sensation (e.g., in the hands, fingers, feet, toes, etc.), loss of bladder or bowel control, and so on.

[0005] Without being bound to any particular theory, it is believed that Cr itself may contribute to the current across the axonal membrane as part of a smaller subgroup of ions included in the Hodgkins-Huxley model for current, shown in equation (1):

(1)

[0006] wherein the lipid bilayer is represented as a capacitance (Cm), voltage-gated and leak ion channels are represented by nonlinear (g_n) and linear ( _L) conductance, respectively, the electrochemical gradients driving the flow of ions are represented by batteries (E), and ion pumps and exchangers are represented by current sources (/_p). Generally, the Hodgkin- Huxley model is a method of modeling current across a neuron membrane based on components of a capacitor. Taking into account the natural ability of a membrane to conduct a charge across two parallel surfaces (e.g., bi-lipid membrane), the more general equation for capacitive current can be used, shown in equation (2):

I=Cm (dv/dt)

(2)

[0007] wherein C_{m i}s the membrane capacitance (ability to store separate charges in the intercellular and extra cellular fluid). The model then accounts for two driving forces that can affect this more basic current; namely the Nernst potential of ions across a membrane (Ei_on) in relation to the membrane potential (V_m) and their corresponding conductance’s (Gi_on). Nemst potential is the potential at which there would be no net movement of an ion due to either its concentration gradient or the electrochemical gradient. Any difference of E _on from Vm (Vm - E_10n) would drive a flow of ions in or out of the ceil membrane and contribute to the total current. This movement is dependent on and proportional to the ions' permeability or conductance across the membrane. The main ions involved in the current seen in the action potential of neurons are Na⁺ and ⁺; however other ions collectively contribute to the total current and are represented in the Hodgkins-Huxley model with an “O”.

[0008] Demyelination decreases the current that can be propagated as it decreases the space between the intra- and extracellular spaces, effectively decreasing the capacitance of the neuron membrane. Cr has the potential to contribute to this last bit of current and/or affect the permeability of Na⁺ and K⁺ to help in the probation of the action potential down the membrane.

[0009] Embodiments may involve a kit including a container to hold a composition including Cr for use as a medicament, a composition including Cr for use in the treatment of debilitating neural diseases such as MS, and so on. A container may be formed of any suitable material such as, for example, a metal material, a polymeric material (e.g., plastic), etc. A container may include a dispenser portion, such as an opening that is accessed via a cap or a nozzle, a film, a perforated surface, and so on. Thus, a container may include a chamber to maintain a composition including Cr, which may be accessed via the dispenser portion of the container for repeated use or for single use (e.g., a vial, a bottle, an bag, etc.).

[0010] A container may be associated with an instruction regarding a composition including Cr composition, such as a storage instruction (e.g., a storage condition), a use instruction (e.g., administration regimen, implant process), a disposal instruction, a warning, and so on. A container may also be associated with information regarding a composition including Cr, such as a chemical formula, a structural formula, a property (e.g., molecular weight, melting point, concentration, etc.), an expiration date, and so on. In one example, a container may include a label to provide an instruction and/or information regarding a composition including Cr, which may also be accessible from data storage such (e.g., computer server, computer readable medium, a database structure, etc.) in any data format (e.g., a text editor format (RTF), an image format (JPEG), a portable document format (PDF), a markup language format (HTTP, XML), a spreadsheet format, etc.). In one example, a label may be physically attached or otherwise associated with a container to provide instructions related to, e.g., an administration regimen. In another example, a container may be a laboratory storage container, a transport container, and so on. In this regard, a label may be physically attached or otherwise associated with a container to provide instructions related to, e.g., suitable storage conditions (e.g., pressure, temperature), hazard warnings, and so on.

[0011] It should be understood that the indefinite articles "a" or "an" carry the meaning of "one or more" or“at least one”. In addition, as used in this application, a list of items joined by the terms“one or more of’,“at least one of’ can mean any combination of the listed terms. For example, the phrases“one or more of A, B and C” and“one or more of A, B or C” can mean A; B; C; A and B; A and C; B and C; or A, B and C. Similarly, a list of terms joined by the term“and so on” or“etc.” can mean the list is not an exhaustive list and may be any combination of the listed terms. For example, the phrase“A, B, C, and so on” can mean A; B; C; A and B; A and C; B and C; or A, B and C.

[0012] Those skilled in the art will appreciate from the foregoing description that the broad techniques of the embodiments may be implemented in a variety of forms. Therefore, while the embodiments have been described in connection with particular examples thereof, the true scope of the embodiments should not be so limited since other modifications will become apparent to the skilled practitioner upon a study of the drawings and the specification described above and/or as follows.

Claims

CLAIMS We claim:

1. A method to treat a neural disease comprising administering a composition including chromium (Cr) in an effective amount to a subject in need thereof.

2. The method of claim 1, wherein the composition is a Chromic Chloride solution.

3. The method of claim 2, wherein the effective amount is about 4 mcg/ml.

4. The method of claim 1, wherein the method includes identifying a type of subject in need thereof.

5. The method of claim 4, wherein the type of subject is a patient having multiple sclerosis (MS) and/or predisposed to having MS.

6. The method of claim 1, wherein the method includes injecting the composition into the cerebrospinal fluid (CSF) of the subject.

7. A kit comprising:

a container;

a composition including chromium (Cr); and

an instruction to administer the composition including Cr in an effective amount to a subject in need of neural disease treatment.

8. The kit of claim 7, wherein the composition is a Chromic Chloride solution.

9. The kit of claim 8, wherein the effective amount is about 4 mcg/ml.

10. The kit of claim 7, wherein the instruction includes to identify a type of subject in need thereof.

11. The kit of claim 10, wherein the type of subject is a patient having multiple sclerosis (MS) and/or predisposed to having MS.

12. The kit of claim 7, wherein the instruction includes to inject the composition into the cerebrospinal fluid (CSF) of the subject.