duelittle2

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duelittle2

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duelittle2

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duelittle2

05/02/24 12:46 PM

Post #46387 on NFT Marketplace Inc (NFTM)

Hotel California

[Verse 6]
Last thing I remember, I was
Running for the door
I had to find the passage back
To the place I was before
"Relax," said the night man
"We are programmed to receive
You can check out any time you like
But you can never leave"

https://genius.com/Eagles-hotel-california-lyrics

duelittle2

05/02/24 12:44 PM

Post #15335 on Digital Locations Inc (DLOC)

I just sent Him this Link 🙃

https://news.satnews.com/2024/02/07/digital-locations-announces-satellite-to-smartphone-antenna-breakthrough/

duelittle2

05/02/24 12:31 PM

Post #15333 on Digital Locations Inc (DLOC)

I think Musk is More on this side of the Equation _ Getting those Sats to be more receptive, which will Help

They are making the antennas on the satellites much bigger in their scramble to turn satellites into cellphone towers.

Companies are also making their satellites more like cellphone towers by flying them lower than before.

Another contributor is improved beamforming, which is how a transmitting device calculates the best way to direct its signal to reach a particular recipient, without interfering with other recipients

https://spectrum.ieee.org/satellite-cellphone-starlink

duelittle2

05/02/24 11:16 AM

Post #15331 on Digital Locations Inc (DLOC)

I thought it was Cool that the News went through SatNews Also - Good Exposure _ imHo

https://news.satnews.com/2024/02/07/digital-locations-announces-satellite-to-smartphone-antenna-breakthrough/

One can sign Up for SatNews by clicking the Link _ Will monitor

duelittle2

05/02/24 10:47 AM

Post #38479 on Cann American Corp (CNNA)

The Check is in the Mail 🙄

duelittle2

05/01/24 10:18 PM

Post #15328 on Digital Locations Inc (DLOC)

https://news.satnews.com/2024/02/07/digital-locations-announces-satellite-to-smartphone-antenna-breakthrough/

https://spectrum.ieee.org/satellite-cellphone-starlink

duelittle2

05/01/24 11:04 AM

Post #15322 on Digital Locations Inc (DLOC)

Chart _ Getting ready for the next leg North _ imo

Surprised this is not over 0.005 yet _ Just needs some Volume

https://www.barchart.com/stocks/quotes/DLOC/technical-chart?plot=CANDLE&volume=total&data=DO&density=M&pricesOn=1&asPctChange=0&logscale=0&indicators=BBANDS(20,2);SMA(20);SRSI(14,20);SMACD(12,26,9);RSI(14,100);ACCUM;STOSL(14,3);SMA(50);SMA(200);ADX(14)&sym=DLOC&grid=1&height=500&studyheight=100

duelittle2

05/01/24 8:18 AM

Post #46370 on NFT Marketplace Inc (NFTM)

"NFT is the brainchild of a diverse and talented group of people from both worlds of art and finance"

Lower left corner _ https://thenftmarketplace.io

🙄🤡

duelittle2

04/30/24 1:37 PM

Post #46359 on NFT Marketplace Inc (NFTM)

They may want to reconsider the Platform

Go where the action is/stay current

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174323737

or

Look for a New Venture _ Cancel the R/S

Why open Up into a Dead market

Perhaps an AI Startup?

xxxxxxxxxxxx

duelittle2

04/30/24 12:46 PM

Post #46356 on NFT Marketplace Inc (NFTM)

The Vast Majority of NFTs are Worthless

Of the 73,257 NFT collections we identified, an eye-watering 69,795 of them have a market cap of 0 Ether (ETH).

This statistic effectively means that 95% of people holding NFT collections are currently holding onto worthless investments. Having looked into those figures, we would estimate that 95% to include over 23 million people who’s investments are now worthless.

https://dappgambl.com/nfts/dead-nfts/

Are NFTs dead?

We analyzed 73,257 NFT collections to find out. #NFT #NFTCollection

Read more here:https://t.co/oFVPpzowEo
— dappGambl (@dappGambl) September 14, 2023

😬

duelittle2

04/29/24 7:53 PM

Post #46346 on NFT Marketplace Inc (NFTM)

NodeMonkes are on top as the leading NFT project over the last week, capped off by a $1 million Bitcoin Ordinals sale. Mar 4, 2024

https://decrypt.co/220107/bitcoin-ordinals-record-1-million-nodemonkes-sale

Someone Just Bought a CryptoPunks NFT for $16 Million in Ethereum Mar 4, 2024

https://decrypt.co/220076/someone-bought-cryptopunks-nft-16-million-ethereum

Solana NFT Marketplace Magic Eden Raises $130M, Plans Multi-Chain Expansion Jun 21, 2022
The top NFT platform on Solana is a newly-minted crypto unicorn with a $1.6 billion valuation—and it’s going to add other blockchains.

https://decrypt.co/103403/solana-nft-marketplace-magic-eden-raises-130m-plans-multi-chain-expansion

TODAY _ https://magiceden.io/bitcoin

XXXXXX

duelittle2

04/29/24 12:38 PM

Post #46343 on NFT Marketplace Inc (NFTM)

Bitcoin Ordinals Are Reshaping the NFT Marketplace Landscape

https://decrypt.co/220154/bitcoin-ordinals-reshaping-nft-marketplace-landscape

https://ordinals.market/

https://magiceden.io/ordinals

You out there Ben🙄

XXXXX

duelittle2

04/29/24 11:56 AM

Post #46342 on NFT Marketplace Inc (NFTM)

NFTs and Ordinals will make a huge comeback.

Non-fungible tokens, or NFTs, have lost much of their cachet since the bull run of 2021-2022. Many of these digital assets, permanently inscribed on the Ethereum blockchain, used to trade hands for millions of dollars. Today, however, an estimated 95 percent of NFTs are “worthless,” according to dappGambl.

Is the market ready for a renaissance? I believe so, though the bitcoin network is fast becoming the preferred platform. One year ago this week, people began inscribing text, images and other media on bitcoin, and by May, it was being reported that the bitcoin blockchain was the second-most popular NFT platform after Ethereum.

Ordinals, as NFTs on the bitcoin network are called, now account for more than half of all daily bitcoin transactions, and trading volumes recently hit a new record high, soaring to $36 million on Dec. 12.

https://irei.com/publications/article/five-bitcoin-and-digital-asset-predictions-for-2024/

$NFTM _ Needs to stay current with the NFT Market Trends/Platforms

xxxxxxxxxxx

duelittle2

04/26/24 2:00 PM

Post #38323 on Cann American Corp (CNNA)

IMO - The Prodigy Post refers to the New Web Page _ Open for Business ?

https://www.prodigyhealthplus.com/

Post did not come from $CNNA

But, trying to be on a positive note _ perhaps getting the Web going, the F10 may not be far behind 🤔

AnyWho _ the Wait goes On

duelittle2

04/23/24 4:24 PM

Post #46278 on NFT Marketplace Inc (NFTM)

The Only reply I can think of is that You could easily be the Poster Child for "Can't Fix Stupid"

Iggy for You

Please return the favor

duelittle2

04/23/24 1:15 PM

Post #46274 on NFT Marketplace Inc (NFTM)

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174102543

duelittle2

04/21/24 1:27 PM

Post #46261 on NFT Marketplace Inc (NFTM)

Let it be given that the A/S is fully Blown out _ 500 Mill O/S Pre-Split

W/ the R/S @ 0.01 = $5 Mill MC And Add in that they raised $5 Mill (prob WAY overvalued)

So Post Split 5 Mill Share O/S w/ a $5 Mill MC @ $1.00

So if they Raised $5 Mill Investment $$ _ How many Restricted Shares would that account for (5 Mill ?) & would they be valued @ $1.00 each

If so, still just a $10 Mill MC w/ 10 Mill O/S ( 5 restricted/5 non-restricted) and 490 mill left in the A/S

This is Just Fuzzy Math, but it seems that no matter how one juggles the numbers - Nothing comes close to $100 Mill MC w/Out significant dilution
even is it Trades @ $1.00 w/out the pps dropping

Peeps are not buying Now @ 0.01, so what will make them buy @ $1.00 w/ no Operational Business/Revs ?

I don't think the FINRA approval alone is enough stimulus to do that

Not saying this Security won't make it, but for many, I think the Break Even/Profit Point will be ~2yrs Post FINRA approval, Just about the Time the resticted shares become Unlocked

JmO

duelittle2

04/20/24 8:09 PM

Post #46255 on NFT Marketplace Inc (NFTM)

The Carrot/Bait was the stating of a MC ~$150 Mill

Right now $0.01 will = $1.00 post R/S

From $1.00 they sell/dump/dilute down ~150 to ~250 Mill shares, Hopefully Not going below $0.50 (0.005 currently) to Attain the MC

Then see how the Platform/Revs go

So what ever One is averaged in At, X that times 100 to Break Even

0.025 Average now will need $2.50pps post split to break even

Weez be F'd _ imO _ Share sell'N machine dressed Up as a NFT Platform

xxxxxxxxxxxxxxxxxxxx

duelittle2

04/18/24 4:38 PM

Post #46234 on NFT Marketplace Inc (NFTM)

I'd be satisfied with a $25+ Mill post split MC

Going to be some "HAT" Trick 🥴 considering where the MC stands Now

duelittle2

04/18/24 1:10 PM

Post #46229 on NFT Marketplace Inc (NFTM)

I opened the Link and it shows 04/30/2024 on my browser _ fwiw

https://website.thenftmarketplace.io/#section-61549c42cacce

Also _ do You mean a $200 Mill MC ?

duelittle2

04/16/24 11:15 AM

Post #43693 on Trump Media and Tech Group (NO Politics Allowed) (DJT)

https://www.barchart.com/stocks/quotes/DJT/technical-chart?plot=CANDLE&volume=total&data=DO&density=O&pricesOn=1&asPctChange=0&logscale=0&indicators=BBANDS%2820%2C2%29%3BSMA%2820%29%3BPTP%2850%29%3BSMA%2850%29%3BSRSI%2814%2C20%29%3BSMACD%2812%2C26%2C9%29%3BRSI%2814%2C100%29%3BACCUM%3BSTOSL%2814%2C3%29%3BSMA%2850%29%3BSMA%28200%29%3BADX%2814%29&sym=DJT&grid=1&height=500&studyheight=100

duelittle2

04/16/24 10:49 AM

Post #5484 on Jaguar Health Inc (JAGX)

https://www.barchart.com/stocks/quotes/JAGX/technical-chart?plot=CANDLE&volume=total&data=DO&density=H&pricesOn=1&asPctChange=0&logscale=0&indicators=BBANDS%2820%2C2%29%3BSMA%2820%29%3BPTP%2850%29%3BSMA%2850%29%3BSRSI%2814%2C20%29%3BSMACD%2812%2C26%2C9%29%3BRSI%2814%2C100%29%3BACCUM%3BSTOSL%2814%2C3%29%3BSMA%2850%29%3BSMA%28200%29%3BADX%2814%29&sym=JAGX&grid=1&height=500&studyheight=100

duelittle2

04/14/24 6:07 PM

Post #15243 on Digital Locations Inc (DLOC)

If DLOC produces a superior product than the One in Use, No reason not to adopt it _ imo

Major carriers could find themselves in a Bidding War🤔

duelittle2

04/14/24 5:03 PM

Post #15241 on Digital Locations Inc (DLOC)

I would guess it depends on who builds the better "Mouse Trap" 🤔

duelittle2

04/14/24 4:28 PM

Post #15239 on Digital Locations Inc (DLOC)

Just saw an AT&T commercial while watching the Masters _ Direct phone to Sat connection coming - fwiw

duelittle2

04/14/24 1:01 PM

Post #46204 on NFT Marketplace Inc (NFTM)

Striper likes Silver too _ tmk

duelittle2

04/14/24 11:39 AM

Post #46201 on NFT Marketplace Inc (NFTM)

https://www.barchart.com/forex/quotes/^XAUUSD/technical-chart?plot=CANDLE&volume=total&data=MO&density=X&pricesOn=1&asPctChange=0&logscale=0&indicators=BBANDS(20%2C2)%3BS

1Kg = 35.27396 oz

duelittle2

04/13/24 2:07 PM

Post #46190 on NFT Marketplace Inc (NFTM)

Is this true? pic.twitter.com/k2yWlrHKzD
— Liz Churchill (@liz_churchill10) April 8, 2024

duelittle2

04/12/24 4:15 PM

Post #46183 on NFT Marketplace Inc (NFTM)

Don't know if Any of Y'all looked @ this Link, but there are many NFT's _ I see near 40 pages🤔

One can Click the Top of Each Column to adjust

MC's have a Wide Range, but some are HUGE

Wonder where NFTM will place and then change to 🤔

https://www.forbes.com/digital-assets/nft-prices/?sh=42bb3e986dfb

xxxxxxxxxxxx

duelittle2

04/11/24 1:30 PM

Post #15233 on Digital Locations Inc (DLOC)

https://www.youtube.com/@digitallocations/shorts

duelittle2

04/11/24 1:04 PM

Post #15232 on Digital Locations Inc (DLOC)

https://www.tomsguide.com/news/starlink-direct-to-cell-satellite-service

https://www.starlink.com/business/direct-to-cell

duelittle2

04/10/24 5:45 PM

Post #38194 on Cann American Corp (CNNA)

ehmm!! "When it goes to a Quarter" 🤑

If it goes to a quarter

duelittle2

04/10/24 12:45 PM

Post #46154 on NFT Marketplace Inc (NFTM)

https://www.forbes.com/digital-assets/nft-prices/?sh=5e14b7926dfb

duelittle2

04/08/24 6:25 PM

Post #46147 on NFT Marketplace Inc (NFTM)

All this Excitement over "Webbed" Feet

duelittle2

04/08/24 2:01 PM

Post #38173 on Cann American Corp (CNNA)

Perhaps bc many are coming to the realization that this Security can be 20X+ this current pps once trading again🤠

duelittle2

04/06/24 2:29 PM

Post #15192 on Digital Locations Inc (DLOC)

https://www.barchart.com/stocks/quotes/DLOC/technical-chart?plot=CANDLE&volume=total&data=WO&density=X&pricesOn=1&asPctChange=0&logscale=1&indicators=BBANDS(20,2);SMA(20);PTP(50);SMA(50);SRSI(14,20);SMACD(12,26,9);RSI(14,100);ACCUM;STOSL(14,3);SMA(50);SMA(200);ADX(14)&sym=DLOC&grid=1&height=500&studyheight=100

duelittle2

04/06/24 1:31 PM

Post #15191 on Digital Locations Inc (DLOC)

Demonstrating the Prototype to Phone manufacturers and getting them to Incorporate the Antenna into their phones will Send this over $1.00 _imHo

“This is a major breakthrough,” said Rich Berliner, CEO of Digital Locations. “Initially we envision SatennaTM in a test phase as an add-on to existing phones. However, if our technology were included in a future version of an Apple iPhone or a Samsung phone, then a user of one of these smartphones of the future could instantly connect to a satellite system offering high-speed Internet service. With total satellite coverage from the sky, the days are numbered for dead zones, dropped calls and slow data.”

https://www.otcmarkets.com/stock/DLOC/news/story?e&id=2758831

https://digitallocations.com/

My Plan _ Buy what I can and Wait _ Risk/Reward _ may take years, may never happen, BUT if it does _ Will be worth it

xxxxxxxxxxxxxxxxxxxxx

duelittle2

04/05/24 12:23 PM

Post #63743 on Integrated Cannabis Solutions Inc (IGPK)

Just a Candle BODY Gap area

Look @ the Other Candles on the way back Up off the drop, Mostly they "Touch"

jMo - May/may not fill

Actually, Mini full Gap 3/28 hi 0.0068 to 04/01 low 0.007, 0.0068 to 0.0070 Micro Gap

https://www.barchart.com/stocks/quotes/IGPK/technical-chart?plot=CANDLE&volume=total&data=DO&density=L&pricesOn=1&asPctChange=0&logscale=0&indicators=BBANDS(20,2);SMA(20);PTP(50);SMA(50);SRSI(14,20);SMACD(12,26,9);RSI(14,100);ACCUM;STOSL(14,3);SMA(50);SMA(200);ADX(14)&sym=IGPK&grid=1&height=500&studyheight=100

duelittle2

04/05/24 12:07 PM

Post #63734 on Integrated Cannabis Solutions Inc (IGPK)

0.0065 TO 0.0077 May Fill _ imo

https://www.barchart.com/stocks/quotes/IGPK/technical-chart?plot=CANDLE&volume=total&data=DO&density=L&pricesOn=1&asPctChange=0&logscale=0&indicators=BBANDS(20,2);SMA(20);PTP(50);SMA(50);SRSI(14,20);SMACD(12,26,9);RSI(14,100);ACCUM;STOSL(14,3);SMA(50);SMA(200);ADX(14)&sym=IGPK&grid=1&height=500&studyheight=100

duelittle2

04/04/24 6:43 PM

Post #25807 on GlobeStar Therapeutics Corp (GSTC)

Yes _ that post came off just looking @ the conventional uses of the main ingredients of the Cocktail

But digging deeper now from a constructive rebuttal

Will attempt to compile some DD on a more positive Note now being enlightened on some 411

We were impressed with the clinical results obtained in Italy for treatment of multiple sclerosis patients using Project Amethyst. These results provide a good foundation for establishing more comprehensive clinical trials with AIP’s partners.

https://multiplesclerosisnewstoday.com/news-posts/2023/06/21/globestar-aip-partner-design-ms-trials-project-amethyst-therapy/

https://www.nationalmssociety.org/For-Professionals/Researchers

---------------------
DETAILED DESCRIPTION OF THE INVENTION

The present invention generally provides for compositions and methods of treating neurodegeneration, and especially multiple sclerosis.

“Neurodegeneration” as used herein, refers to any condition that results in loss of structure and/or function of neurons, especially in the CNS and/or peripheral nervous system. The composition of the present invention can be used to treat neurodegenerative diseases characterized by a demyelinating form and/or intoxication, or the presence of viruses such as Epstein Barr virus or other members of the same family of herpesviruses, and especially multiple sclerosis. Other demyelinating neurodegenerative disease can include, but are not limited to, myelinoclastic disorders (Devic's disease, inflammatory demyelinating diseases), leukodystrophic disorders (CNS neuropathies, central pontine myelinolysis, myelopathies (Tabes dorsalis), leukoencephalopathies (progressive multifocal leukoencephalopathy), and leukodystrophies), Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, anti-MAG peripheral neuropathy, Charcot-Marie-Tooth disease, copper deficiency associated conditions, and progressive inflammatory neuropathy. Preferably, the neurodegeneration causes lesions and demyelination of nerves.
“Multiple sclerosis” as used herein, can refer to autoimmune-type relapsing-remitting, progressive, or degenerative forms of multiple sclerosis.
“Recovering mobility” as used herein refers to recovering at least some, and preferably most or all, use of limbs and extremities such that an individual can move without as much restriction and/or pain as previously as well as with more control. Preferably, recovering mobility includes recovering the ability to walk and balance without aids such as a walker, cane, or assistance of an individual.
The composition of the present invention includes an antibiotic, an antifungal agent, and a lipophilic potentiating agent in synergistically effective amounts. More preferably, the composition includes a tetracycline antibiotic, a triazole antifungal agent, and a lipophilic statin in synergistically effective amounts. Even more preferably, the composition includes minocycline, fluconazole, and atorvastatain. Preferably, the composition is a pharmaceutical composition including pharmaceutically acceptable excipients.
The antibiotic can be any suitable antibiotic and is preferably a tetracycline antibiotic. Most preferably, the tetracycline antibiotic is minocycline ((2E,4S,4aR,5aS,12aR)-2-(amino-hydroxy-methylidene)-4,7-bis(dimethylamino)-10,11,12a-trihydroxy-4a,5,5a,6-tetrahydro-4H-tetracene-1,3,12-trione). Minocycline is long-acting and has a longer half-life than other tetracyclines. Minocycline is lipid soluble and easily penetrates the brain and CNS. Any other equivalent forms can be used. Other tetracycline antibiotics with the same function that can be used include, but are not limited to, tetracycline, chlortetracycline, oxytetracycline, demeclocycline, methacycline, tigecycline, or doxycycline. In general, tetracycline antibiotics act to inhibit protein synthesis and the binding of aminoacyl-tRNA to the mRNA-ribosome complex. The dose of the tetracycline antibiotic can be from 25 mg to 500 mg, every 12 hours, depending on age and weight. Preferably, the dose is from 50 mg to 100 mg. Most preferably, the dose is 100 mg. It should be understood that a lower dose can be used because of the synergy of the components.
The antifungal agent can be any suitable antifungal agent, and preferably, a triazole antifungal agent or acycloguanosine (2-Amino-1,9-dihydro-9-((2-hydroxyethoxy)methyl)-6H-purin-6-one), also known as aciclovir. The triazole antifungal agent is preferably fluconazole. Fluconazole is an antifungal agent with a triazole ring structure (2-(2,4-Difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol). The presence of the substituent triazole increases the selectivity of the drug for fungal cytochrome P450 (lower toxicity for humans), water solubility, and resistance to degradation compared to imidazole derivatives. Fluconazole acts by interfering with synthesis of the fungal cell membrane by inhibiting cytochrome P450 enzyme 14a-demethylase. It causes inhibition of the enzyme lanosterol 14-demethylase C thus blocking the synthesis of ergosterol, one of the main constituents of the fungal cell membrane. Failure of the formation of ergosterol causes an increase in membrane permeability followed by cell death. It is active both in vitro and in vivo against Candida spp. (C. albicans, C. glabrata, C. tropicalis, C lusitaniae, kirusci C., C. parapsilosis, C. guilliermandi); about 90% of the isolated strains of Candida were susceptible to concentrations of fluconazole of from 0.25 to 6.4 mg/L. Typically, fluconazole acts as a fungistatic (replication inhibitor) toward typical Candida. Fluconazole is an effective drug in the treatment of localized and systemic fungal infections typically incurred by Candida, the overgrowth of which is a known effect of broad-spectrum antibiotics, as well as other fungal pathogens. Any other equivalent forms can be used. Other triazole antifungal agents with the same function that can be used include, but are not limited to, albaconazole, efinaconazole, isavuconazole, itraconazole, voriconazole, pramiconazole, ravuconazole, terconazole, or posaconazole. The dose of the triazole antifungal agent can be 25 mg to 400 mg every 12 hours, depending on age and weight. Preferably, the dose is between 50 mg and 100 mg. Most preferably, the dose of the triazole antifungal agent is 50 mg. It should be understood that a lower dose can be used because of the synergy of the components.
The lipophilic potentiating agent can be any suitable agent that is able to cross the blood-brain barrier. Preferably, the lipophilic potentiating agent is a lipophilic statin. The lipophilic statin is preferably atorvastatin (LIPITOR®, Pfizer) ((3R,5R)-7-[2-(4-Fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid). Atorvastatin is a competitive inhibitor of HMG-CoA reductase, reducing cholesterol. Lipophilic statins are effective at crossing the blood-brain barrier into the CNS. Any other equivalent forms can be used. Other lipophilic statins with the same function that can be used include, but are not limited to, lovastatin, simvastatin, cerivastatin, fluvastatin, and mevastatin. The dose of the lipophilic statin can be 5 mg to 40 mg every 12 hours, depending on age and weight. Most preferably, the dose is 20 mg, or even 10 mg in order to avoid rhabdomyolysis. It should be understood that a lower dose can be used because of the synergy of the components.
Preferably, the composition is in a single oral dosage form, such as a pill, capsule, or tablet, with each of the antibiotic, antifungal agent, and lipophilic potentiating agent contained therein or within a coating. Different combinations or each component can be included within the oral dosage form or within its coating. The composition can be tailored to provide different release profiles as needed or desired for a particular patient, such as, but not limited to, sustained release, prolonged release, or immediate release. The antibiotic, antifungal agent, and lipophilic potentiating agent can each have the same release profiles or different release profiles. However, other dosage forms and routes can be used as detailed below. Preferably, the dosage form is gastroresistant.
Acycloguanosine can also be administered in combination with the recommended daily allowance of Vitamin D for its immunomodulatory properties believed to reverse the immune-deficiencies found in patients with autoimmune diseases.
The preferred combination of components in the composition is 100 mg minocycline, 20 mg atorvastatin, and 50 mg fluconazole in a single dosage form.
Preferably, the composition is administered once every 12 hours, considering the half-lives of the components. Other times of administration can be used depending on the dosage. While beneficial effects can be experienced upon taking the first dose, it is preferred that an individual continue treatment for days, weeks, months, and/or years. Treatment can be 45 days or longer, Length and frequency of treatment is contingent upon the form of disease, i.e., primary progressive or relapsing-remitting.
The three components of the composition (antibiotic, antifungal agent, and lipophilic potentiating agent) produce a potentiated effect as opposed to their effect alone because they act synergistically together. This can result in a lower dose of each component required to be effective and reduced side effects. In the examples below, no noteworthy side effects were experienced. The combination of an antibiotic and the lipophilic potentiating agent implement the elimination and eradication of capsids immortalized by a consequent inflammatory process and induce a regenerative process of injured areas. In order to reduce the potential, albeit reduced, toxicity from the prolonged ingestion of tetracycline antibiotics, it is necessary to add an antifungal agent for its fungistatic properties. The combination of minocycline, atorvastatin, and fluconazole was chosen because of the low toxicity of the same, high ability to pass the blood-brain barrier, the same half-life of the drugs, and the ability to interact synergistically with each other. The ability to penetrate into the tissues of atorvastatin lipid allows, if it is administered in conjunction with a suitable excipient, to boost the ability of the immune modulating minocycline and to increase the neuroprotective ability of the statin. The antifungal agent was added to reduce the presence of fungi, or the proliferation of the same in an environment overloaded from antibiotic such as minocycline, or already infested by appearances such as Candida albicans. Often the presence of fungi is high due to previous infections brought by the imbalance caused by the massive use of corticosteroids, immunosuppressants, and the like, which already by themselves would be eligible to trigger a mechanism of excessive proliferation of the same that, once past the blood brain barrier through the presence of the same into the blood stream, are able to trigger a mechanism of systemic intoxication and amplify the inflammatory process. In particular, fluconazole is the preferred antifungal agent due its the half-life being equal to that of atorvastatin and minocycline and it acts primarily in the lipophilic environment. Fluconazole was able to enhance the synergistic effect of the atorvastatin and minocycline combination, therefore producing a synergistic effect with all three components of the composition of the present invention.
The compounds of the present invention are administered and dosed in accordance with good medical practice, taking into account the clinical condition of the individual patient, the site and method of administration, scheduling of administration, patient age, sex, body weight and other factors known to medical practitioners. The pharmaceutically “effective amount” for purposes herein is thus determined by such considerations as are known in the art. The amount must be effective to achieve improvement including but not limited to improved survival rate or more rapid recovery, or improvement or elimination of symptoms and other indicators as are selected as appropriate measures by those skilled in the art.
In the method of the present invention, the compound of the present invention can be administered in various ways. It should be noted that it can be administered as the compound and can be administered alone or as an active ingredient in combination with pharmaceutically acceptable carriers, diluents, adjuvants and vehicles. The compounds can be administered orally, subcutaneously or parenterally including intravenous, intraarterial, intramuscular, intraperitoneally, intratonsillar, and intranasal administration as well as intrathecal and infusion techniques. Implants of the compounds are also useful. The patient being treated is a warm-blooded animal and, in particular, mammals including man. The pharmaceutically acceptable carriers, diluents, adjuvants and vehicles as well as implant carriers generally refer to inert, non-toxic solid or liquid fillers, diluents or encapsulating material not reacting with the active ingredients of the invention.
The doses can be single doses or multiple doses over a period of several days. The treatment generally has a length proportional to the length of the disease process and drug effectiveness and the patient species being treated.
When administering the compound of the present invention parenterally, it will generally be formulated in a unit dosage injectable form (solution, suspension, emulsion). The pharmaceutical formulations suitable for injection include sterile aqueous solutions or dispersions and sterile powders for reconstitution into sterile injectable solutions or dispersions. The carrier can be a solvent or dispersing medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils.
Proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Nonaqueous vehicles such a cottonseed oil, sesame oil, olive oil, soybean oil, corn oil, sunflower oil, or peanut oil and esters, such as isopropyl myristate, may also be used as solvent systems for compound compositions. Additionally, various additives which enhance the stability, sterility, and isotonicity of the compositions, including antimicrobial preservatives, antioxidants, chelating agents, and buffers, can be added. Prevention of the action of microorganisms can be ensured by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, and the like. In many cases, it will be desirable to include isotonic agents, for example, sugars, sodium chloride, and the like. Prolonged absorption of the injectable pharmaceutical form can be brought about by the use of agents delaying absorption, for example, aluminum monostearate and gelatin. According to the present invention, however, any vehicle, diluent, or additive used would have to be compatible with the compounds.
Sterile injectable solutions can be prepared by incorporating the compounds utilized in practicing the present invention in the required amount of the appropriate solvent with various of the other ingredients, as desired.
A pharmacological formulation of the present invention can be administered to the patient in an injectable formulation containing any compatible carrier, such as various vehicle, adjuvants, additives, and diluents; or the compounds utilized in the present invention can be administered parenterally to the patient in the form of slow-release subcutaneous implants or targeted delivery systems such as monoclonal antibodies, vectored delivery, iontophoretic, polymer matrices, liposomes, and microspheres. Examples of delivery systems useful in the present invention include: U.S. Pat. Nos. 5,225,182; 5,169,383; 5,167,616; 4,959,217; 4,925,678; 4,487,603; 4,486,194; 4,447,233; 4,447,224; 4,439,196; and 4,475,196. Many other such implants, delivery systems, and modules are well known to those skilled in the art.
The present invention provides for a method of treating neurodegeneration, by administering a synergistically effective amount of a composition including an antibiotic, antifungal agent, and lipophilic potentiating agent to an individual suffering from neurodegeneration. The neurodegeneration can be caused by any disease described above, and especially multiple sclerosis. Preferably, the antibiotic is a tetracycline antibiotic, the antifungal agent is a triazole antifungal agent, and the lipophilic potentiating agent is a lipophilic statin. Most preferably, the tetracycline antibiotic is minocycline, the triazole antifungal agent is fluconazole, and lipophilic statin is atorvastatin. The antibiotic, antifungal agent, and lipophilic potentiating agent can also be any of those described above. Preferably, the composition is administered in a single dosage form orally once every 12 hours. Preferably, the single dosage form includes 100 mg minocycline, 20 mg atorvastatin, and 50 mg fluconazole. Treatment can last 45 days or longer.
Treating neurodegeneration, especially multiple sclerosis, can include reducing and/or eliminating symptoms experienced with neurodegeneration as well as reversing the cause of neurodegeneration. As further demonstrated in the examples below, the composition of the present invention can reduce and/or eliminate symptoms of neurodegeneration and multiple sclerosis such as by improving and recovering mobility and motor control in limbs and extremities, decreasing fatigue and increasing energy levels, improving and restoring balance, improving and restoring the ability to walk and be upright, improving and restoring urinary and bowel control, reducing muscle pain, and reducing and eliminating paresthesia. Any combination of these improvements can be experienced by the individual depending on their symptoms when beginning treatment. The composition of the present invention can also reduce lesions (in size and amount) in the central nervous system and/or peripheral nervous system that cause neurodegeneration, especially multiple sclerosis. The method can reduce an individual's EDSS value by at least two points.
The present invention therefore also provides for a method of reducing and/or eliminating symptoms of neurodegeneration, by administering a synergistically effective amount of a composition including an antibiotic, antifungal agent, and lipophilic potentiating agent to an individual suffering from neurodegeneration, and reducing and/or eliminating the individual's symptoms of neurodegeneration. The neurodegeneration can be caused by any disease described above, and especially multiple sclerosis. The composition can be any of those described above. Preferably, the composition is administered in a single dosage form orally. Preferably, the single dosage form includes 100 mg minocycline, 20 mg atorvastatin, and 50 mg fluconazole. The symptoms reduced and/or eliminated are described above.
The present invention also provides for a method of reducing and/or eliminating lesions from neurodegeneration, by administering a synergistically effective amount of a composition including an antibiotic, antifungal agent, and lipophilic potentiating agent to an individual suffering from neurodegeneration, and reducing and/or eliminating lesions in the central nervous system and/or peripheral nervous system. The neurodegeneration can be caused by any disease described above, and especially multiple sclerosis. The composition can be any of those described above. Preferably, the composition is administered in a single dosage form orally as described above. Preferably, the single dosage form includes 100 mg minocycline, 20 mg atorvastatin, and 50 mg fluconazole. Preferably, the lesions are reduced at least 40%, and more preferably, at least 50%. Reducing the lesions results in a recovery of function of the body and a reduction/elimination of the symptoms of multiple sclerosis. In other words, the composition is able to remyelinate damaged nerves (i.e. demyelinated nerves) in the CNS that have been damaged due to neurodegeneration.
The present invention provides for a method of recovering mobility of an individual suffering from neurodegeneration, by administering a synergistically effective amount of a composition including an antibiotic, antifungal agent, and lipophilic potentiating agent to the individual, and recovering mobility and motor control in the individual's limbs and extremities. The neurodegeneration can be caused by any disease described above, and especially multiple sclerosis. The composition can be any of those described above. Preferably, the composition is administered in a single dosage form orally as described above. Preferably, the single dosage form includes 100 mg minocycline, 20 mg atorvastatin, and 50 mg fluconazole. Preferably, mobility and motor control is increased enough such that the individual can walk and balance without aid.
In preliminary mice studies, MS was induced in mice as experimental autoimmune encephalomyelitis (EAE) and administration of atorvastatin and minocycline let to improvements clinically and immunologically. There was a significant anti-inflammatory and neuroprotective activity. Severity and histological consequences were reduced and progression of the disease was slowed. This was confirmed by a visible reduction of the areas of brain lesion by 40%.
While atorvastatin and minocycline were synergistic, additional synergism was experienced when fluconazole was added in experiments detailed below in MS human subjects. These MS subjects showed significant functional recovery as early as the first week of administration, through 45 days (extending over the time of suspending the therapy) confirmed by the administration of test and evaluation boards (Scale Bartel Index, analysis of muscle imbalance, Kendall, and two minute walking test (2MWT)). An increase in efficacy was experienced when the combination of three compounds was used. The use of fluconazole reduced the side effect nearly to zero of an increase in abdominal volume likely caused by the use of prolonged minocycline, which as an antibiotic may have produced an increase in the proliferation of Candida albicans. None of the patients experienced negative reactions with any medication already used, and none had any relapse during the treatment.
To date, all subjects involved have a significant improvement in quality of life and recovered much autonomy. In one subject, it has been observed through magnetic resonance that there was a remission of demyelinated areas of approximately 40%.
The composition of the present invention is advantageous in that each component individually has been proven effective, and in combination produces a synergistic effect not shown before in MS patients. Each component has low toxicity and a long period of permanence in the market. The composition is effective in reducing the incidence of MS on quality of life of the patient. Further, no relapses have been experienced by subjects in the examples below.
The invention is further described in detail by reference to the following experimental examples. These examples are provided for the purpose of illustration only, and are not intended to be limiting unless otherwise specified. Thus, the invention should in no way be construed as being limited to the following examples, but rather, should be construed to encompass any and all variations which become evident as a result of the teaching provided herein.

https://patents.google.com/patent/US10610592B2/en

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