153 replies to this topic

[Hux]

What about serrapeptase, I'm sure there was some kind of study done a while back.

[sagafemina]

Re: Pomegranates

 

Tried to quote and got a pageful so deleted them all.

 

It appears that pomegranate has MANY potent health effects.  See http://www.ncbi.nlm....pubmed/24800189

 

And the juice is delicious, easy to find now and not expensive. 

 

I think I will be substituting it for any other red juice (had been using aronia berry) in my black tea red wine iced tea concoction. 

 

 

Edited by sagafemina, 19 April 2015 - 01:47 AM.

[Daniel Cooper]

Ok for this answer you owe me your first born male child (ala rumplestiltskin) . If the kid is a jerk forget it!

 

I have been drinking pomegranate juice ever since reading about an experiment where rats were given the equivalent of 4 oz of pomegranate juice a day for 6 weeks. They had a 14% reduction of plaque in 6 weeks. 

 

I read about an experiment where compromised men who drank one cup a day for one year had an average reduction of laque in the carotid of 34%.

I suggested this to a friend. She had a 40% reduction of plaque in the carotid in 8 months. 

 

Unless you have diabetes risk to reward is probably minor.

 

I do this. 

 

How was this reduction verified?  Was it a reduction in calcified plaques?

Edited by Daniel Cooper, 17 March 2016 - 06:22 AM.

[aaCharley]

 

Ok for this answer you owe me your first born male child (ala rumplestiltskin) . If the kid is a jerk forget it!

 

I have been drinking pomegranate juice ever since reading about an experiment where rats were given the equivalent of 4 oz of pomegranate juice a day for 6 weeks. They had a 14% reduction of plaque in 6 weeks. 

 

I read about an experiment where compromised men who drank one cup a day for one year had an average reduction of laque in the carotid of 34%.

I suggested this to a friend. She had a 40% reduction of plaque in the carotid in 8 months. 

 

Unless you have diabetes risk to reward is probably minor.

 

I do this. 

 

How was this reduction verified?  Was it a reduction in calcified plaques?

 

 

Sorry I cannot get the link to paste.  Life Extension has a pretty good write up on pomegranate juice.  The Israeli study from several years ago showed a 30% reduction in plaque after one year of dosing with about two ounces daily.  Other markets also improved.  Trial was on 12 elderly patients with over 80% blockage and nonsmokers.
 

Edited by aaCharley, 29 March 2016 - 10:38 PM.

[Darryl]

Injections of 2-hydroxypropyl-β-cyclodextrin (probably Kleptose® HPB from Roquette):

 

Zimmer et al. 2016. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming. Science Translational Medicine. 8(333), pp. 333

Continuous retention of apolipoprotein B–containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Because cholesterol accumulation and deposition of cholesterol crystals (CCs) trigger a complex inflammatory response, we tested the efficacy of the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound that increases cholesterol solubility in preventing and reversing atherosclerosis. We showed that CD treatment of murine atherosclerosis reduced atherosclerotic plaque size and CC load and promoted plaque regression even with a continued cholesterol-rich diet. Mechanistically, CD increased oxysterol production in both macrophages and human atherosclerotic plaques and promoted liver X receptor (LXR)–mediated transcriptional reprogramming to improve cholesterol efflux and exert anti-inflammatory effects. In vivo, this CD-mediated LXR agonism was required for the antiatherosclerotic and anti-inflammatory effects of CD as well as for augmented reverse cholesterol transport. Because CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis.

 

Edited by Darryl, 08 April 2016 - 06:35 AM.

[Daniel Cooper]

 

Injections of 2-hydroxypropyl-β-cyclodextrin (probably Kleptose® HPB from Roquette):

 

Zimmer et al. 2016. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming. Science Translational Medicine. 8(333), pp. 333

Continuous retention of apolipoprotein B–containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Because cholesterol accumulation and deposition of cholesterol crystals (CCs) trigger a complex inflammatory response, we tested the efficacy of the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound that increases cholesterol solubility in preventing and reversing atherosclerosis. We showed that CD treatment of murine atherosclerosis reduced atherosclerotic plaque size and CC load and promoted plaque regression even with a continued cholesterol-rich diet. Mechanistically, CD increased oxysterol production in both macrophages and human atherosclerotic plaques and promoted liver X receptor (LXR)–mediated transcriptional reprogramming to improve cholesterol efflux and exert anti-inflammatory effects. In vivo, this CD-mediated LXR agonism was required for the antiatherosclerotic and anti-inflammatory effects of CD as well as for augmented reverse cholesterol transport. Because CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis.

 

 

 

This is potentially an important paper that deserves some attention.

 

Question:  Does cyclodextrin make it through the GI tract intact in enough quantity to establish a decent plasma level so that oral administration is viable, or is injection the only practical route?

Edited by Daniel Cooper, 12 April 2016 - 02:22 PM.

[YOLF]

Ok for this answer you owe me your first born male child (ala rumplestiltskin) . If the kid is a jerk forget it!

 

I have been drinking pomegranate juice ever since reading about an experiment where rats were given the equivalent of 4 oz of pomegranate juice a day for 6 weeks. They had a 14% reduction of plaque in 6 weeks. 

 

I read about an experiment where compromised men who drank one cup a day for one year had an average reduction of laque in the carotid of 34%.

I suggested this to a friend. She had a 40% reduction of plaque in the carotid in 8 months. 

 

Unless you have diabetes risk to reward is probably minor.

 

I do this. 

You could drink it with a generous helping of (cooked) cannellini beans.

[YOLF]

 

 

Phosphatidylcholine is an approved medication for the treatment of atherosclerosis in Euorpe.

 

It is known by plaquex, essentiale, or lipostabil

 

I grimace because the phosphatidylcholine might be breaking down to constituents, which include unfortunately omega-6 fatty acids.   What's the mechanism of action?

 

 

 

Ummm -- there don't need to be omega - 6 fatty acids in phosphatidylcholine

 

Phosphatidylcholine can contain palmitoleic acid (omega -7) as the saturated fatty acid ; and oleic acid as the unsaturated fatty acid ( omega -9)

 

http://en.wikipedia....phatidylcholine

 

Can they do the Omega 7 without an Omega 9?

[YOLF]

 

 

 

I did a quick search on Pubmed and came up dry.  I suppose they could refer to pomegranate by a different scientific name?  I tried to cross reference against arterial, carotid, heart, etc.   I have seen the claim made on naturopathic blogs, so I am hoping there is some real research too.

 

Does anyone know of a freeze dried source for pomegranate?   It's extremely seasonal, and it's really hard to get the seeds out of the compartments.

 

 

Found this: http://www.ncbi.nlm....C4007340/#ref15
 

 

The references in that study are great, but I think you misquoted the one that is relevant to the current thread on reducing existing arterial plaque formations.   The one that is amazing is this reference:

http://www.sciencedi...261561403002139

http://www.ncbi.nlm....pubmed/15158307

 

The results are very dramatic, and the patients were only consuming about 50 ml of juice per day.  But that was a concentrate, and the footnote in the study refers to some other study to understand how that concentrate was prepared.  If someone is motivated to follow through on that let us all know how many pomegranate seeds you have to juice to get an approximately equivalent concentration of polyphenols.

 

The bad part of this study is that patients were largely on one or more other therapies like statins.  So we cannot rule out potential interactions and synergies between different therapies and the pomegranate juice.

 

Still, it makes me want to add in some pomegranate seeds to my breakfast every morning.   How much is enough?

 

Thanks for that reference!

 

So what kind of pomegranate (seed) extract does one look for?

[YOLF]

 

Injections of 2-hydroxypropyl-β-cyclodextrin (probably Kleptose® HPB from Roquette):

 

Zimmer et al. 2016. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming. Science Translational Medicine. 8(333), pp. 333

Continuous retention of apolipoprotein B–containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Because cholesterol accumulation and deposition of cholesterol crystals (CCs) trigger a complex inflammatory response, we tested the efficacy of the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound that increases cholesterol solubility in preventing and reversing atherosclerosis. We showed that CD treatment of murine atherosclerosis reduced atherosclerotic plaque size and CC load and promoted plaque regression even with a continued cholesterol-rich diet. Mechanistically, CD increased oxysterol production in both macrophages and human atherosclerotic plaques and promoted liver X receptor (LXR)–mediated transcriptional reprogramming to improve cholesterol efflux and exert anti-inflammatory effects. In vivo, this CD-mediated LXR agonism was required for the antiatherosclerotic and anti-inflammatory effects of CD as well as for augmented reverse cholesterol transport. Because CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis.

 

Can it be taken as a pill?

[YOLF]

 

 

Injections of 2-hydroxypropyl-β-cyclodextrin (probably Kleptose® HPB from Roquette):

 

Zimmer et al. 2016. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming. Science Translational Medicine. 8(333), pp. 333

Continuous retention of apolipoprotein B–containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Because cholesterol accumulation and deposition of cholesterol crystals (CCs) trigger a complex inflammatory response, we tested the efficacy of the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound that increases cholesterol solubility in preventing and reversing atherosclerosis. We showed that CD treatment of murine atherosclerosis reduced atherosclerotic plaque size and CC load and promoted plaque regression even with a continued cholesterol-rich diet. Mechanistically, CD increased oxysterol production in both macrophages and human atherosclerotic plaques and promoted liver X receptor (LXR)–mediated transcriptional reprogramming to improve cholesterol efflux and exert anti-inflammatory effects. In vivo, this CD-mediated LXR agonism was required for the antiatherosclerotic and anti-inflammatory effects of CD as well as for augmented reverse cholesterol transport. Because CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis.

 

 

 

This is potentially an important paper that deserves some attention.

 

Question:  Does cyclodextrin make it through the GI tract intact in enough quantity to establish a decent plasma level so that oral administration is viable, or is injection the only practical route?

 

What about being absorbed topically? Is it right to assume that we have these CCs in our skin and other tissues?

[YOLF]

Correction: Details on synephrine

[Daniel Cooper]

 

 

 

Injections of 2-hydroxypropyl-β-cyclodextrin (probably Kleptose® HPB from Roquette):

 

Zimmer et al. 2016. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming. Science Translational Medicine. 8(333), pp. 333

Continuous retention of apolipoprotein B–containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Because cholesterol accumulation and deposition of cholesterol crystals (CCs) trigger a complex inflammatory response, we tested the efficacy of the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound that increases cholesterol solubility in preventing and reversing atherosclerosis. We showed that CD treatment of murine atherosclerosis reduced atherosclerotic plaque size and CC load and promoted plaque regression even with a continued cholesterol-rich diet. Mechanistically, CD increased oxysterol production in both macrophages and human atherosclerotic plaques and promoted liver X receptor (LXR)–mediated transcriptional reprogramming to improve cholesterol efflux and exert anti-inflammatory effects. In vivo, this CD-mediated LXR agonism was required for the antiatherosclerotic and anti-inflammatory effects of CD as well as for augmented reverse cholesterol transport. Because CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis.

 

 

 

This is potentially an important paper that deserves some attention.

 

Question:  Does cyclodextrin make it through the GI tract intact in enough quantity to establish a decent plasma level so that oral administration is viable, or is injection the only practical route?

 

What about being absorbed topically? Is it right to assume that we have these CCs in our skin and other tissues?

 

 

I'm not sure where else cholesterol crystals also show up.  They certainly get the most attention in the vascular system where they are a major component of coronary artery disease.

 

Hopefully someone with a better background in this will be along, but I'd be surprised if you'd be able to get a decent sized molecule like cyclodextrin delivered in significant quantities transdermally.  Maybe sublingually? 

 

We know that subcutaneous injection works (that's what they used in the mouse studies).  Maybe you could get enough through the digestive system to be useful.  I have seen at least one study that did measure blood plasma levels after oral administration, so some of it makes it through.  I just don't have a way to compare the plasma levels achieved in the mouse study with what you might achieve orally.

[YOLF]

How much did they have to take for the oral administration? I suppose the stuff is cheap. How stable is it?

 

I suppose subQ inj wouldn't be unmanageable... still I tend not to want to take needles daily.

[YOLF]

Maybe something like this?

https://www.aerosphe....com/video.html

[YOLF]

http://www.archiveso...CGOTLA>2.0.CO;2

 

 

[micro2000]

This is a very interesting study for the fact that they used subQ injections and not intravenous, but the doses are huge:  2g/kg BW twice weekly.  This rounds out to be 10 grams of cyclodextrin, for a 60 kg person, injected subQ twice weekly or 2-3 grams per day.  One problem with the paper is that I cannot find out how they solubilized the cyclodextrin and the concentration, though CD is very water soluble, so phosphate buffered saline should suffice.

 

Cyclodextrins are huge molecular weight molecules, so oral administration is unlikely to achieve any significant plasma levels due to poor bioavailability.  Transdermal would be worse, I suspect.

[Daniel Cooper]

This is a very interesting study for the fact that they used subQ injections and not intravenous, but the doses are huge:  2g/kg BW twice weekly.  This rounds out to be 10 grams of cyclodextrin, for a 60 kg person, injected subQ twice weekly or 2-3 grams per day.  One problem with the paper is that I cannot find out how they solubilized the cyclodextrin and the concentration, though CD is very water soluble, so phosphate buffered saline should suffice.

 

Cyclodextrins are huge molecular weight molecules, so oral administration is unlikely to achieve any significant plasma levels due to poor bioavailability.  Transdermal would be worse, I suspect.

 

 

Do we get to apply the normal scaling to convert between a mouse model to a human to those dosages, i.e. divide by 12.3?

[Daniel Cooper]

Here's a toxicology review that has some pharmacokinetics.

 

2-Hydroxypropyl-b-cyclodextrin (HP-b-CD): A toxicology review

 

http://addiandcassi....logy-review.pdf

 

They also conclude low bio-availability via the oral route, essentially measuring no plasma levels one hour after oral administration. 

 

Looks to me like subcutaneous is your best bet.

 

So, can we scale those doses they used in the mouse study by the normal mouse -> human translation (i.e. divide by 12.3)?

 

Could a compounding pharmacy make something appropriate for injection up for you?

 

 

[Daniel Cooper]

Cyclodextrin molecules are relatively large (molecular weight ranging from almost 1000 to > 2000 Da) with a large number of hydrogen donors and acceptors, and are consequently poorly absorbed through biological membranes. The natural α- and β-cyclodextrin, unlike γ-cyclodextrin, cannot be hydrolysed by human salivary and pancreatic amylases [19,20], but all three are subjected to fermentation by the intestinal microflora. Hydrophilic cyclodextrins are non-toxic at low to moderate oral dosages [11,15]. The natural cyclodextrins and their derivatives are used in topical and oral formulations, but only α-cyclodextrin and the hydrophilic derivatives of β- and γ-cyclodextrin can be used in parenteral formulations. γ-Cyclodextrin forms visible aggregates in aqueous solutions and, thus, is not well suited for parenteral formulations [21]. Due to its nephrotoxicity, β-cyclodextrin cannot be used in parenteral formulations.

 

From this source:  https://notendur.hi....tlo/general.pdf

 

 

The last sentence in that paragraph is a bit troubling.  Did the mouse paper use a hydrophilic derivative of beta cyclodextin?

 

 

 

 

 

 

[micro2000]

Cyclodextrin molecules are relatively large (molecular weight ranging from almost 1000 to > 2000 Da) with a large number of hydrogen donors and acceptors, and are consequently poorly absorbed through biological membranes. The natural α- and β-cyclodextrin, unlike γ-cyclodextrin, cannot be hydrolysed by human salivary and pancreatic amylases [19,20], but all three are subjected to fermentation by the intestinal microflora. Hydrophilic cyclodextrins are non-toxic at low to moderate oral dosages [11,15]. The natural cyclodextrins and their derivatives are used in topical and oral formulations, but only α-cyclodextrin and the hydrophilic derivatives of β- and γ-cyclodextrin can be used in parenteral formulations. γ-Cyclodextrin forms visible aggregates in aqueous solutions and, thus, is not well suited for parenteral formulations [21]. Due to its nephrotoxicity, β-cyclodextrin cannot be used in parenteral formulations.

 

From this source:  https://notendur.hi....tlo/general.pdf

 

 

The last sentence in that paragraph is a bit troubling.  Did the mouse paper use a hydrophilic derivative of beta cyclodextin?

 

The paper addressed this.  They use 2-hydroxypropyl-beta CD which hasn't shown the same nephrotoxicity issues.

[micro2000]

Here's a toxicology review that has some pharmacokinetics.

 

2-Hydroxypropyl-b-cyclodextrin (HP-b-CD): A toxicology review

 

http://addiandcassi....logy-review.pdf

 

They also conclude low bio-availability via the oral route, essentially measuring no plasma levels one hour after oral administration. 

 

Looks to me like subcutaneous is your best bet.

 

So, can we scale those doses they used in the mouse study by the normal mouse -> human translation (i.e. divide by 12.3)?

 

Could a compounding pharmacy make something appropriate for injection up for you?

 

12.3 is a close approximation for mouse to human.  I'm not sure if you could get a pharmacy to prepare this, due to legality issues, but making a sterile PBS based cyclodextrin solution wouldn't be difficult.  My concern is the solubility limits for such a preparation, since it wasn't elaborated in the paper.  There is not a single compound called 2-HP-b-CD, but various products that differ by the number of 2-hydroxypropyl groups attached to the exterior of the cyclodextrin.  Higher hydroxypropyl additions equals greater water solubility, but generally higher price.  Few would wish to inject 5-10 mL of saline daily.

[Daniel Cooper]

 

Here's a toxicology review that has some pharmacokinetics.

 

2-Hydroxypropyl-b-cyclodextrin (HP-b-CD): A toxicology review

 

http://addiandcassi....logy-review.pdf

 

They also conclude low bio-availability via the oral route, essentially measuring no plasma levels one hour after oral administration. 

 

Looks to me like subcutaneous is your best bet.

 

So, can we scale those doses they used in the mouse study by the normal mouse -> human translation (i.e. divide by 12.3)?

 

Could a compounding pharmacy make something appropriate for injection up for you?

 

12.3 is a close approximation for mouse to human.  I'm not sure if you could get a pharmacy to prepare this, due to legality issues, but making a sterile PBS based cyclodextrin solution wouldn't be difficult.  My concern is the solubility limits for such a preparation, since it wasn't elaborated in the paper.  There is not a single compound called 2-HP-b-CD, but various products that differ by the number of 2-hydroxypropyl groups attached to the exterior of the cyclodextrin.  Higher hydroxypropyl additions equals greater water solubility, but generally higher price.  Few would wish to inject 5-10 mL of saline daily.

 

 

Ah, I see you already did the mouse -> human translation when you arrived at your 10g dose.

 

Yes, a very high dose indeed.

 

Did the paper say what molarity solution they used?

[micro2000]

 

Here's a toxicology review that has some pharmacokinetics.

 

2-Hydroxypropyl-b-cyclodextrin (HP-b-CD): A toxicology review

 

http://addiandcassi....logy-review.pdf

 

They also conclude low bio-availability via the oral route, essentially measuring no plasma levels one hour after oral administration. 

 

Looks to me like subcutaneous is your best bet.

 

So, can we scale those doses they used in the mouse study by the normal mouse -> human translation (i.e. divide by 12.3)?

 

Could a compounding pharmacy make something appropriate for injection up for you?

 

12.3 is a close approximation for mouse to human.  I'm not sure if you could get a pharmacy to prepare this, due to legality issues, but making a sterile PBS based cyclodextrin solution wouldn't be difficult.  My concern is the solubility limits for such a preparation, since it wasn't elaborated in the paper.  There is not a single compound called 2-HP-b-CD, but various products that differ by the number of 2-hydroxypropyl groups attached to the exterior of the cyclodextrin.  Higher hydroxypropyl additions equals greater water solubility, but generally higher price.  Few would wish to inject 5-10 mL of saline daily.

 

http://www.ncbi.nlm....pubmed/26404254

 

From the above paper, they give the details of the CD preparation used.  A 20% w/v solution of 2HP-b-CD.  At 200mg/mL this would be impractical for the normal person to attempt injecting 14-15mL of saline per day.

[Daniel Cooper]

Just skimmed the whole paper.  I would really like to read that Methods and Materials reference section but don't have access.

[micro2000]

4. Experimental Section 4.1. Mice, Diet and Injections

The mice were housed under standard conditions and given free access to food and water. All experiments were approved by the Committee for Animal Welfare of Maastricht University and performed according to Dutch regulations. Eleven to twelve-week old female Ldlr−/− mice on a C57/Bl6 background were either fed regular chow (n = 10) or an HFC diet (n = 12 per HFC group with and without HP-B-CD treatment) for 12 weeks. The effects of HP-B-CD were investigated by giving weekly subcuteanous injections at the start of the HFC diet with 4000 mg per kg of body weight of 20% w/v HP-B-CD (H107, Sigma-Aldrich GmbH, St. Louis, MO, USA) (n = 12). PBS was used for control injections. The HFC diet contained 21% milk butter, 0.2% cholesterol, 46% carbohydrates and 17% casein. Collection of blood and tissue specimens, biochemical determination of lipids in plasma, liver histology, electron microscopy, acid phosphatase (ACPase) enzyme cytochemistry, RNA isolation, complementary DNA synthesis and quantitative polymerase chain reaction were determined as described previously [4,5,38,39,40,41]. Pieces of liver were used for quantification of liver cholesterol and the hepatic levels of campesterol and 7α-hydroxycholesterol as described previously [42].

 

Note:  this second paper uses 4g/kg BW, whereas the other paper used 2g/kg BW.

Edited by micro2000, 13 April 2016 - 09:56 PM.

[Daniel Cooper]

 

 

Here's a toxicology review that has some pharmacokinetics.

 

2-Hydroxypropyl-b-cyclodextrin (HP-b-CD): A toxicology review

 

http://addiandcassi....logy-review.pdf

 

They also conclude low bio-availability via the oral route, essentially measuring no plasma levels one hour after oral administration. 

 

Looks to me like subcutaneous is your best bet.

 

So, can we scale those doses they used in the mouse study by the normal mouse -> human translation (i.e. divide by 12.3)?

 

Could a compounding pharmacy make something appropriate for injection up for you?

 

12.3 is a close approximation for mouse to human.  I'm not sure if you could get a pharmacy to prepare this, due to legality issues, but making a sterile PBS based cyclodextrin solution wouldn't be difficult.  My concern is the solubility limits for such a preparation, since it wasn't elaborated in the paper.  There is not a single compound called 2-HP-b-CD, but various products that differ by the number of 2-hydroxypropyl groups attached to the exterior of the cyclodextrin.  Higher hydroxypropyl additions equals greater water solubility, but generally higher price.  Few would wish to inject 5-10 mL of saline daily.

 

http://www.ncbi.nlm....pubmed/26404254

 

From the above paper, they give the details of the CD preparation used.  A 20% w/v solution of 2HP-b-CD.  At 200mg/mL this would be impractical for the normal person to attempt injecting 14-15mL of saline per day.

 

 

You might double the concentration (maybe), but even at that 7 ml is a substantial volume of fluid for subcutaneous injection.

 

Of course, we don't know how they arrived at that dose or what the effective dose threshold is.

[micro2000]

 

 

 

Here's a toxicology review that has some pharmacokinetics.

 

2-Hydroxypropyl-b-cyclodextrin (HP-b-CD): A toxicology review

 

http://addiandcassi....logy-review.pdf

 

They also conclude low bio-availability via the oral route, essentially measuring no plasma levels one hour after oral administration. 

 

Looks to me like subcutaneous is your best bet.

 

So, can we scale those doses they used in the mouse study by the normal mouse -> human translation (i.e. divide by 12.3)?

 

Could a compounding pharmacy make something appropriate for injection up for you?

 

12.3 is a close approximation for mouse to human.  I'm not sure if you could get a pharmacy to prepare this, due to legality issues, but making a sterile PBS based cyclodextrin solution wouldn't be difficult.  My concern is the solubility limits for such a preparation, since it wasn't elaborated in the paper.  There is not a single compound called 2-HP-b-CD, but various products that differ by the number of 2-hydroxypropyl groups attached to the exterior of the cyclodextrin.  Higher hydroxypropyl additions equals greater water solubility, but generally higher price.  Few would wish to inject 5-10 mL of saline daily.

 

http://www.ncbi.nlm....pubmed/26404254

 

From the above paper, they give the details of the CD preparation used.  A 20% w/v solution of 2HP-b-CD.  At 200mg/mL this would be impractical for the normal person to attempt injecting 14-15mL of saline per day.

 

 

You might double the concentration (maybe), but even at that 7 ml is a substantial volume of fluid for subcutaneous injection.

 

Of course, we don't know how they arrived at that dose or what the effective dose threshold is.

 

There are 2HP-b-CD products that show high solubility (70% w/v), but I wonder what the viscosity of such a preparation would be.

[YOLF]

There was a human case study... what kind of dosing was used there?

[Daniel Cooper]

There was a human case study... what kind of dosing was used there?

 

I haven't seen a human case study doing CD for the reduction of arterial plaques.  If you've seen such a study please post it, I'd love to see that.

 

I have seen a study were they were using it to treat Niemann-Pick disease.  If I recall they were doing IV infusion of pretty massive doses.  I think ultimately they were planning on doing intrathecal infusion since CD doesn't cross the BBB.  Apparently the FDA has licensed this treatment for Niemann-Pick on a compassionate use basis.