U.S. patent application number 15/914249 was filed with the patent office on 2018-07-19 for compositions and methods for obtaining an improved lung function.
The applicant listed for this patent is PHARMALUNDENSIS AB. Invention is credited to Staffan Skogvall.
Application Number | 20180200292 15/914249 |
Document ID | / |
Family ID | 51945878 |
Filed Date | 2018-07-19 |
United States Patent
Application |
20180200292 |
Kind Code |
A1 |
Skogvall; Staffan |
July 19, 2018 |
COMPOSITIONS AND METHODS FOR OBTAINING AN IMPROVED LUNG
FUNCTION
Abstract
A pharmaceutical composition for obtaining an improved lung
function in a human or an animal lung affected by airway
obstruction such as COPD or asthma, is provided. The composition
comprises a pharmacologically effective amount of activated carbon
comprising adsorbed iodine and/or an adsorbed iodide salt and a
sodium/iodide symporter inhibitor, such as perchlorate.
Additionally, a method for obtaining an improved lung function in a
human or animal lung affected by airway obstruction, such as COPD
or asthma, is provided. The method comprises the steps of
administering a pharmacologically effective amount of activated
carbon comprising adsorbed iodine and/or an adsorbed iodide salt,
and administering a sodium/iodide symporter inhibitor, such as
perchlorate, in connection to the administration of the
pharmacologically effective amount of activated carbon comprising
adsorbed iodine and/or an adsorbed iodide salt.
Inventors: |
Skogvall; Staffan; (Lund,
SE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
PHARMALUNDENSIS AB |
Lund |
|
SE |
|
|
Family ID: |
51945878 |
Appl. No.: |
15/914249 |
Filed: |
March 7, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15036953 |
May 16, 2016 |
9943542 |
|
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PCT/EP2014/075098 |
Nov 20, 2014 |
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15914249 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 33/20 20130101;
A61P 11/00 20180101; A61K 9/0053 20130101; A61K 33/18 20130101;
A61K 33/44 20130101; A61K 45/06 20130101; A61P 43/00 20180101; A61K
33/00 20130101; A61P 11/06 20180101; A61K 9/501 20130101; A61K
33/44 20130101; A61K 2300/00 20130101; A61K 33/18 20130101; A61K
2300/00 20130101; A61K 33/00 20130101; A61K 2300/00 20130101 |
International
Class: |
A61K 33/20 20060101
A61K033/20; A61K 9/50 20060101 A61K009/50; A61K 9/00 20060101
A61K009/00; A61K 33/44 20060101 A61K033/44; A61K 33/18 20060101
A61K033/18; A61K 33/00 20060101 A61K033/00; A61K 45/06 20060101
A61K045/06 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 20, 2013 |
SE |
1351373-4 |
Claims
1. A pharmaceutical composition for obtaining an improved lung
function in a human or an animal lung affected by chronic
obstructive pulmonary disease (COPD) or asthma, comprising: a
pharmacologically effective amount of activated carbon comprising
adsorbed iodine (I.sub.2) and/or an adsorbed iodide salt; and
perchlorate.
2. (canceled)
3. The pharmaceutical composition according to claim 1, wherein the
ratio of adsorbed iodine and/or iodide salt and perchlorate is in
the range of 200:1 to 1:5.
4. The pharmaceutical composition according to claim 1, wherein the
ratio of adsorbed iodine and/or iodide salt and perchlorate is in
the range of 100:1 to 1:1.
5. The pharmaceutical composition according to claim 1, wherein the
amount of perchlorate is in the range of from 1 mg to 1000 mg.
6. The pharmaceutical composition according to claim 1, wherein the
amount of perchlorate is in the range of from 25 mg to 500 mg.
7. The pharmaceutical composition according to claim 1, wherein the
amount of perchlorate is in the range from 50 mg to 250 mg.
8. (canceled)
9. The pharmaceutical composition according claim 1, wherein the
amount of activated carbon comprising adsorbed iodine and/or an
adsorbed iodide salt and perchlorate is from 0.10 g to 500 g.
10. The pharmaceutical composition according to claim 1, wherein
the amount of activated carbon comprising adsorbed iodine and/or an
adsorbed iodide salt and perchlorate is from 0.5 g to 100 g.
11. The pharmaceutical composition according to claim 1, wherein
the amount of activated carbon comprising adsorbed iodine and/or an
adsorbed iodide salt and perchlorate is from 1 g to 25 g.
12. The pharmaceutical composition according to claim 1, wherein
the adsorbed iodide salt is an alkali metal iodide or earth alkali
metal iodide salt.
13. The pharmaceutical composition according to claim 1, wherein
the perchlorate is in the form of a perchlorate salt.
14. The pharmaceutical composition according to claim 1, wherein
the pharmaceutical composition is a pharmaceutical composition for
oral administration.
15. (canceled)
16. (canceled)
17. (canceled)
18. The pharmaceutical composition according to claim 1, for
obtaining an improved lung function in a human or an animal lung
affected by chronic obstructive pulmonary disease (COPD) or asthma,
administered in a dosage regimen of 0.10 g to 500 g daily.
19. A kit for obtaining an improved lung function in a human or an
animal lung affected by chronic obstructive pulmonary disease
(COPD) or asthma, comprising: a first pharmaceutical composition,
comprising a pharmacologically effective amount of activated carbon
comprising adsorbed iodine and/or an adsorbed iodide salt; and a
second pharmaceutical composition, comprising perchlorate.
20. (canceled)
21. A method for obtaining an improved lung function in a human or
an animal lung affected by chronic obstructive pulmonary disease
(COPD) or asthma, comprising the steps of: administering to the
human or animal a pharmacologically effective amount activated
carbon comprising adsorbed iodine and/or an adsorbed iodide salt;
and administering perchlorate in connection to the administration
of the pharmacologically effective amount of activated carbon
comprising adsorbed iodine and/or an adsorbed iodide salt.
22-23. (canceled)
24. The method according to claim 21, comprising administering to
the human or animal the pharmaceutical composition according to
claim 1.
25. The method according to claim 21, wherein the administration of
the pharmacologically effective amount of activated carbon
comprising adsorbed iodine and/or an adsorbed iodide salt is oral
administration to the human or animal.
26. The method according to claim 21, wherein the administration of
the perchlorate is oral administration to the human or animal.
Description
FIELD OF THE INVENTION
[0001] The present invention pertains to a pharmaceutical
composition for obtaining an improved lung function in a human or
an animal lung affected by airway obstruction. Additionally, the
present invention pertains to pharmaceutical compositions for use
in treatment of chronic obstructive pulmonary disease and/or
asthma, and methods for obtaining an improved lung function in a
human or animal lung affected by airway obstruction.
BACKGROUND OF THE INVENTION
[0002] Chronic obstructive pulmonary disease (COPD), which is also
known as chronic obstructive lung disease (COLD), chronic
obstructive airway disease (COAD), chronic airflow limitation
(CAL), and chronic obstructive respiratory disease (CORD), is a
lung disease which primary symptoms include persistent obstruction
in the airways, shortness of breath, cough, and sputum
production.
[0003] COPD is often associated with tobacco smoking and is
characterized by inflammation in the airways and a gradual decline
in lung function. As the disease progresses during many years, the
airway obstruction can become very severe, leading to extreme
dyspnea during both exercise and rest and, eventually, lung
failure. At this stage, lung function examinations with spirometry
usually reveal a loss of lung capacity by 50% or more. Other severe
symptoms often appear at this time as well, such as weight loss,
depression and cardiac disease. The mortality risk is high in these
patients. The established pharmaceutical treatments for these
patients are anti-cholinergics, beta2-agonists and steroids, which
however normally only give minor improvements. Causing over 3
million deaths in 2011, COPD is ranked as the fourth leading cause
of death worldwide (World Health Organization. "The top 10 causes
of death". Fact sheet No 310. July 2013). Due to the aging
population mortality is expected to increase in many countries. The
economic burden of COPD in the U.S. was estimated at $42.6 billion
in health care costs and lost productivity during 2007. Thus, there
is urgent need for new and effective treatments for COPD.
[0004] Asthma is characterized by chronic inflammation of the
airways with mainly reversible airway obstruction and bronchial
hyper-reactivity. Asthma is thought to be the result of a
combination of genetic and environmental factors. Asthma is usually
treatable with steroids and bronchodilators, however, 10% of
asthmatics have severe symptoms in spite of maximum treatment.
There is also an overlap between COPD and asthma, often rendering a
firm diagnosis difficult to obtain (Chang, J.; Mosenifar, Z.
"Differentiating COPD from Asthma in Clinical Practice". Journal of
Intensive Care Medicine, 2007, vol. 22, 300-309]).
[0005] There have also been reports about obstructive pulmonary
diseases, mainly asthma, in animals such as cats and dogs. As in
humans, these animals get an obstruction of the airways when the
bronchi fill up with mucous and go into spasms
(bronchoconstriction). It is far more common in cats than dogs, and
particularly in Siamese and Himalayan cat breeds
(AnimalHospitals-USA, 2007).
[0006] Iodides have been used for many years as expectorants, for
instance potassium iodide. However, clinical efficacy of these
substances has not been conclusively demonstrated and they may
induce thyroid disease (Rogers D F. "Mucoactive drugs for asthma
and COPD: any place in therapy?" Expert Opin. Investig. Drugs. 2002
January;11(1):15-35). Iodinated glycerol has been suggested as a
potentially less toxic product, but clinical trials have shown it
to lack significant improvement in pulmonary function following 16
weeks treatment with iodinated glycerol. Long term use has also
been connected with side effects such as iodine poisoning (Rubin B
K. et.al. "Iodinated glycerol has no effect on pulmonary function,
symptom score, or sputum properties in patients with stable chronic
bronchitis." Chest. 1996 February;109(2):348-52).
[0007] Iodine is a vital element found in two hormones in humans;
thyroxine (T4) and triiodothyronine (T3). They stimulate the body
including growth and development. Iodine is actively pumped into
the thyroid cells by the sodium/iodide symporter (also called
iodide pump or Na+-I- pump) and T4 and T3 regulate metabolism.
Furthermore, it has recently been shown that the active uptake of
iodide in the intestine is caused by this pump. "Am J Physiol Cell
Physiol. 2009 April;296(4):C654-62. doi: 10.115/ajpcell.00509.2008.
The sodium/iodide symporter is also responsible for absorption of
iodide in the kidney, which prevents loss of iodide in the
urine.
[0008] Activated carbon is known for treating poisoning and as an
adjunct to diet for occasional diarrhoea. Medical coal efficiently
binds a large number of toxins and may thus prevent harmful
substances such as pharmaceuticals, chemicals and bacterial toxins
into the body. Activated charcoal has a very large surface area; 1
gram has a surface area of 300-2000 m.sup.2 (GREENWOOD, N. N.
et.al. "Chemistry of the Elements" Pergamon Press 1984). The term
activated carbon also comprises what is meant by the term activated
charcoal. Impregnated activated charcoals are carbonaceous
adsorbents which have chemicals finely distributed on their
internal surface. The impregnation optimizes the existing
properties of the activated charcoal giving a synergism between the
chemicals and the charcoal (Carbo Tech-Aktivkohlen GmbH.
Franz-Ficher-Weg, vol. 61, D-45307, Germany).
[0009] It has been shown that iodinated activated charcoal (IAC)
can improve lung function on patients with COPD (Skogvall). In EP 2
222 314 B1 is disclosed a method of treating COPD by using iodine
on activated carbon. The iodinated activated carbon is administered
orally, and it is shown that the carbon or iodine alone does not
improve the lung function. Only when iodine was adsorbed on the
activated charcoal was there an improved lung function.
[0010] Recently, a "Proof of concept" clinical study has confirmed
the positive effects by IAC on the lung function of COPD patients,
with a significant improvement of the pulmonary function (FEV.sub.1
baseline, Forced Expiratory Volume in 1 second) in patients who
received IAC, but not placebo. However, the improvement of lung
function was only moderate (average 8.2% better than placebo after
the 8 week treatment).
[0011] It was felt that it should be possible to improve the lung
function even further, and it was therefore examined if additional
substances could improve the lung function even more.
SUMMARY OF THE INVENTION
[0012] Accordingly, the present invention discloses that a
combination of activated carbon comprising adsorbed iodine
(I.sub.2) and/or an adsorbed iodide salt and an inhibitor of the
sodium/iodide symporter surprisingly causes a synergistic
improvement of the lung function of individuals with pulmonary
obstruction.
[0013] When IAC was taken together with the sodium/iodide symporter
inhibitor potassium perchlorate, there was an almost doubling of
the improvement of the lung function (FEV.sub.1) compared to when
IAC was taken alone. Also, the combination (IAC+perchlorate)
reduced the patient's problems with cough and sputum more than when
only IAC was given. This synergistic effect by adding perchlorate
to IAC is very surprising, because perchlorate reduces the
absorption of iodide from the intestine. If the effect by IAC
somehow was that iodine has a direct positive effect on the
airways, one would expect that a reduced absorption of iodide from
the intestine would result in a reduced positive effect on the
airways. Also, use of only perchlorate did not improve the lung
function at all. Thus, the combination of IAC and perchlorate
apparently results in a synergistic improvement of the lung
function, compared to when IAC and perchlorate are taken as single
treatment.
[0014] For these purposes a pharmaceutical composition for
obtaining an improved lung function in a human or an animal lung
affected by airway obstruction is provided, such as COPD or asthma,
said composition comprising a pharmacologically effective amount of
activated carbon comprising adsorbed iodine and/or an adsorbed
iodide salt and a sodium/iodide symporter inhibitor.
[0015] Additionally, a method for obtaining an improved lung
function in a human or animal lung affected by airway obstruction,
such as COPD or asthma, is provided, said method comprising the
steps of administering a pharmacologically effective amount of
activated carbon comprising adsorbed iodine and/or an adsorbed
iodide salt, and administering a sodium/iodide symporter inhibitor
in connection to the administration of the pharmacologically
effective amount of activated carbon comprising adsorbed iodine
and/or an adsorbed iodide salt.
[0016] Further advantageous features of the invention are defined
in the dependent claims. In addition, advantageous features of the
invention are elaborated in embodiments disclosed herein.
DESCRIPTION OF PREFERRED EMBODIMENTS
[0017] A pharmacologically effective amount of activated carbon
comprising adsorbed iodine and/or an adsorbed iodide salt in
combination with a sodium/iodide symporter inhibitor for producing
improvement of lung function is described.
[0018] It has previously been found that treatment of COPD patients
for 8 weeks with IAC only resulted in a moderate increase of lung
function (8.2% increase of FEV.sub.1 baseline compared to placebo).
However, it has now surprisingly been found that addition of a
sodium/iodide symporter inhibitor (potassium perchlorate) gives a
further synergistic improvement of the lung function.
[0019] Perchlorated is known to be a powerful sodium/iodide
symporter inhibitor (ClO.sub.4.sup.-). Perchlorate functions as a
competitive inhibitor of the sodium/iodide symporter (NIS) wich
controls the iodide uptake in the intestine, thyroid gland, and
kidneys. Studies have shown that already low levels of above 0.007
milligrams per kilogram a day (mg/(kgd)) perchlorate can
temporarily inhibit the thyroid gland's ability to adsorb iodine
from the bloodstream (Greer, M. A. et.al "Health effect assessment
for environmental perchlorate contamination: The dose response for
inhibition of thyroidal radioiodide uptake in humans".
Environmental Health Perspectives 110 (9): 927-937, 2002).
Perchlorate is neither metabolised nor stored in the body (J.
Wolff. "Perchlorate and the Thyroid Gland". Pharmacological Reviews
1998 50 (1): 89-105.)
[0020] Thiocyanate (SCN.sup.-) is also a sodium/iodide symporter
inhibitor. While the relative potency of thiocyanate for inhibiting
iodide uptake by the sodium/iodide symporter is lower than that of
perchlorate on a molar concentration basis in serum, it offers an
alternative sodium/iodide symporter inhibitor for an individual
where perchlorate is unsuitable (Tonacchera M. et.al. "Relative
potencies and additivity of perchlorate, thiocyanate, nitrate and
iodide on the inhibition of radioactive iodide uptake by the human
sodium/iodide symporter." Thyroid 2004: 14:1012-1019). Other
possible sodium/iodide symporter inhibitors include nitrate
(NO.sub.3.sup.-), perrhenate (ReO.sub.4.sup.-), hydrogen phosphate
(HPO.sub.4.sup.2-), fluoride (F), sulfate (SO.sub.4.sup.2-), and
pharmaceutically acceptable salts thereof, dysidenin, isodysidenin,
HMA [5-(N,N -hexamethylene)amiloride], DMA
[5-(N,N-dimethyl)amiloride], econazole, miconazole, ketoconazole
and terconazole. A preferred sodium/iodide symporter inhibitor is
perchlorate or nitrate.
[0021] The present invention discloses the use of a
pharmacologically effective amount of activated carbon comprising
iodine and/or an adsorbed iodide salt in combination with a
sodium/iodide symporter inhibitor, such as perchlorate, in the
manufacture of a medicament for producing an improved lung function
in the lungs of a human or an animal with chronic obstructive
pulmonary disease (COPD) or asthma.
[0022] It has been thought that iodide perhaps is responsible for
the beneficial effect of IAC by directly influencing the airways in
a human or an animal lung affected by airway obstruction. However,
the discovery that the combination of IAC and perchlorate has a
synergistic positive effect on lung function, in spite of
perchlorate reducing the intestinal uptake of iodide, is contrary
to the belief of the skilled person in the art.
[0023] Preferred administration forms for the pharmaceutical
composition of the invention are pharmaceutical compositions for
oral intake, such as tablets, tablets with disintegrants, capsules
which disintegrate relatively fast in the stomach such as gelatin
capsules and pullulan capsules, standard capsules (gelatine,
vegetable or pullulan), wherein the tablets and capsules comprise
activated carbon comprising adsorbed iodine and/or an adsorbed
iodide salt and optionally comprise a sodium/iodide symporter
inhibitor, such as perchlorate and any of flavor, colour,
preservative, sweetener excipient.
[0024] Preferred iodine or iodide salt concentration is from 1% to
20% w/w of the activated charcoal, in particular from 3% to 17% w/w
of the activated charcoal, most preferred from 5 to 13 w/w of the
activated charcoal.
[0025] Daily doses to a human of iodine and/or iodide salt
administered in form of the pharmaceutical composition are from 5
mg to 5,000 mg, in particular from 25 mg to 1,000 mg, most
preferred from 50 mg to 500 mg.
[0026] Doses administered to a human of activated carbon comprising
adsorbed iodine and/or an adsorbed iodide salt are from 0.10 g to
500 g daily, in particular from 0.5 g to 100 g daily, most
preferred from 1 g to 25 g daily.
[0027] Daily doses to a human of sodium/iodide symporter inhibitor,
such as perchlorate, administered in form of the pharmaceutical
composition are from 1 mg to 1000 mg, in particular from 25 mg to
500 mg, most preferred from 50 mg to 250 mg.
[0028] The daily doses to a human of sodium/iodide symporter
inhibitor, such as perchlorate, adsorbed iodine and/or iodide salt
and activated carbon comprising adsorbed iodine and/or an adsorbed
iodide salt, according to above, may be combined, such that
perchlorate is administered in form of the pharmaceutical
composition from 1 mg to 1000 mg, in particular from 25 mg to 500
mg, most preferred from 50 mg to 250 mg, while adsorbed iodine
and/or iodide salt is administered from 5 mg to 5,000 mg, in
particular from 25 mg to 1,000 mg, most preferred from 50 mg to 500
mg, and activated carbon comprising adsorbed iodine and/or an
adsorbed iodide salt are from 0.10 g to 500 g daily, in particular
from 0.5 g to 100 g daily, most preferred from 1 g to 25 g
daily.
[0029] Perchlorate can be in the form of a perchlorate salt, such
as sodium perchlorate and potassium perchlorate. Thiocyanate can be
in the form of a thiocyanate salt, such as potassium thiocyanate
and sodium thiocyanate. Nitrate can be in the form of a thiocyanate
salt, such as potassium nitrate (KNO.sub.3) and sodium nitrate
(NaNO.sub.3).
[0030] The adsorbed iodide salt may be selected from a group of
alkali metal iodides and earth alkali iodides. Typical examples of
such iodides that could be used in the present invention are NaI,
KI, MgI.sub.2, and CaI.sub.2.
[0031] The ratio between the adsorbed iodine and/or iodide salt in
the activated carbon comprising adsorbed iodine and/or iodide salt
and the sodium/iodide symporter inhibitor may be selected to be in
the interval from 200:1 to 1:5. When the sodium/iodide symporter
inhibitor is perchlorate, thus the ratio between the adsorbed
iodine and/or iodide salt in the activated carbon comprising
adsorbed iodine and/or iodide salt and perchlorate may be selected
to be in the interval from 200:1 to 1:5. The ratio between the
adsorbed iodine and/or iodide salt in the activated carbon
comprising adsorbed iodine and/or iodide salt and the sodium/iodide
symporter inhibitor may even more preferably be selected to be in
the interval from 100:1 to 1:1. When the sodium/iodide symporter
inhibitor is perchlorate, thus the ratio between the adsorbed
iodine and/or iodide salt in the activated carbon comprising
adsorbed iodine and/or iodide salt and perchlorate may even more
preferably be selected to be in the interval from 50:1 to 1:1.
[0032] The activated carbon comprising adsorbed iodine and/or an
adsorbed iodide salt and sodium/iodide symporter inhibitor, such as
perchlorate, may be administered to the intestine of a human or an
animal in need of an improved lung function, in a pharmaceutically
acceptable form, in particular in form of a tablet or capsule
comprising elemental iodine/iodide salt on activated charcoal.
[0033] The activated carbon comprising adsorbed iodine and/or an
adsorbed iodide salt and a sodium/iodide symporter inhibitor may be
administered to the intestine of a human or an animal in form of a
tablet, wherein the tablet comprises disintegrant for fast release
of the tablet contents in the stomach.
[0034] The activated carbon comprising adsorbed iodine and/or an
adsorbed iodide salt and sodium/iodide symporter inhibitor, such as
perchlorate, may be administered to the intestine of a human or an
animal in form of a capsule, wherein the capsule shell is comprised
by gelatin or pullulan for fast release of the capsule contents, or
a vegetable capsule.
[0035] The activated carbon comprising adsorbed iodine and/or an
adsorbed iodide salt and sodium/iodide symporter inhibitor, such as
perchlorate, may be administered to the intestine of a human or an
animal in the form of a capsule, wherein the capsule shell is
comprised by gelatin or pullulan or a vegetable capsule.
[0036] The activated carbon comprising adsorbed iodine (I.sub.2)
and/or an adsorbed iodide salt and a sodium/iodide symporter
inhibitor may be administered in the same formulated tablet(s) or
capsule(s) or in separate tablets or capsules. In one example, the
activated carbon comprising adsorbed iodine and/or an adsorbed
iodide salt and sodium/iodide symporter inhibitor are administered
to the intestine of a human or an animal, in the same tablet(s) or
capsule(s), following the daily dosing regimes as previously
described. In another example, the activated carbon comprising
adsorbed iodine and/or an adsorbed iodide salt and sodium/iodide
symporter inhibitor are administered to the intestine of a human or
an animal, in different tablets or capsules, following the daily
dosing regimes as previously described, with the advantage of
better control of any undesired interactions or effects between the
sodium/iodide symporter inhibitor and activated carbon comprising
adsorbed iodine and/or an adsorbed iodide salt in the stomach or
intestine. Furthermore, the activated carbon powder comprising
adsorbed iodine and/or an adsorbed iodide salt can be poured in a
glass of water and drunk, while the sodium/iodide symporter
inhibitor can either be placed in the water or a capsule or
tablet.
[0037] The activated carbon comprising adsorbed iodine and/or an
adsorbed iodide salt and a sodium/iodide symporter inhibitor can be
supplied as a kit for obtaining an improved lung function in a
human or an animal lung affected by airway obstruction, comprising
a first pharmaceutical composition, comprising a pharmacologically
effective amount of activated carbon comprising adsorbed iodine
and/or an adsorbed iodide salt; and a second pharmaceutical
composition, comprising a sodium/iodide symporter inhibitor.
EXAMPLES
Example 1
Preparation of Activated Carbon Samples Loaded Alkali Metal Iodide
or Earth Alkali Metal Iodide
[0038] Materials:
[0039] Activated carbon (Sigma C7606), Potassium iodide (Sigma
P7744), deionized water.
[0040] Equipment:
[0041] Magnetic stirrer IKA RTC basic, oil bath, reflux condenser,
balance XP-300 (Denver instruments), Pyrex glass flask (2 L),
polymer-enclosed magnetic bar, vacuum filter flask (2 L), OOH
filter paper (Whatman), laboratory drying oven TS80000,
Termaks.
[0042] Method:
[0043] 8.0 g KI was dissolved in 1 L of water in an adsorption
experiment. Activated carbon (92 g) was added. The suspension was
stirred for 12 hours at room temperature (21-23.degree. C.). The
activated carbon product was separated from the KI solution by
filtration under reduced pressure and dried for 12 h in 75.degree.
C. This resulted in a sample consisting of activated carbon
impregnated with .about.1.6% (wt.) KI. Activated carbon
preparations coated with other specific amounts of KI were obtained
by repeating example 1 using other amounts of activated carbon and
KI. Determination of the amount of adsorbed KI on activated carbon
was carried out by three methods, namely conductometry, gravimetric
analysis and elemental analysis.
Example 2
Preparation of Iodinated Activated Carbon
[0044] Materials: Activated carbon from Sigma C7606; meets USP
testing specification. Elemental Iodine from Sigma-Aldrich 03002;
meets USP testing. Undenatured ethanol from Kemetyl; meets USP and
EP testing specifications with <0.5% water content.
[0045] Equipment:
[0046] Mixing cylinder 500 ml, measuring cylinder 500 ml, E-flask
50 ml, Buchner funnel Duran diameter 105 ml and stirrer motor with
blade, RZR 1 from Heidolph. Filterpaper grade 00H from Munktell.
Evaporation dish made from borosilicate glass.
[0047] Method: Depending on the batch size, the amount of activated
carbon, elemental iodine and ethanol is calculated. For a batch
size of 50 g iodinated carbon, 4.5 g of iodine, 45.5 g of activated
carbon and 450 ml ethanol is used. The activated carbon is
suspended in the measuring cylinder with 410 ml ethanol and the
elemental iodine is solved in the E-flask with 40 ml ethanol. The
iodine is added, stirred for 2 min and allowed to impregnate the
carbon for 1 h. Thereafter, the iodinated activated carbon is
separated from the ethanol solution by filtration under reduced
pressure and dried for 5 hours at 150.degree. C. This results in
iodinated activated carbon impregnated with 9% (wt.) I.sub.2. The
amount of adsorbed iodine is determined by elemental analysis.
Example 3
Clinical Effect by IAC on Patients with Moderate COPD
[0048] The effect of 8 weeks treatment with oral iodinated
activated charcoal (IAC) on lung function of patients with moderate
chronic obstructive pulmonary disease (COPD) was examined in a
double blind randomized placebo controlled parallel group study
with 40 patients. In the IAC group, patients showed a statistically
significant improvement of FEV.sub.1 baseline by 130 ml compared to
placebo, corresponding to 8.2% improvement (p=0.031*). Correlation
statistics revealed that the improvement of FEV.sub.1 baseline was
significantly correlated both to FEV.sub.1 post-bronchodilator
(p=0.0020**) and FEV.sub.1 post-exercise (0.0328*) values, which
demonstrates that the positive effect by IodoCarb is present also
on top of a bronchodilator and that patients do not reach a limit
for maximal improvement of the lung function. In summary, this
study demonstrates that iodinated activated charcoal surprisingly
and significantly improved lung function of patients with moderate
COPD.
Example 4
Effect by a Combination of Activated Carbon Comprising Adsorbed
Iodine and an Inhibitor of the Sodium/Iodide Symporter on Lung
Function
[0049] An 80-year old Caucasian man with moderately severe COPD
examined the synergistic effect by a combination of IAC and
potassium perchlorate. After having stable lung function for around
a month, he took 2,73 g activated charcoal in water daily for 2
weeks. This did not improve his lung function (FEV.sub.1). After
that, he instead took 270 mg I.sub.2 daily in a vegetable capsule
daily for 2 weeks. This did not improve his lung function.
Thereafter, he instead took 100 mg potassium perchlorate daily for
2 weeks. This did not improve the lung function at all. Following
this, he instead took 3 g IAC (prepared according to example 2, and
consisting of 2.73 g activated charcoal with 270 mg iodine) daily
for 2 weeks. This improved his lung function (FEV.sub.1) by 150 ml.
Finally, he took a combination of 100 mg potassium perchlorate and
3 g IAC daily for 2 weeks. This improved his FEV.sub.1 by 270 ml.
Thus, a combination of IAC and perchlorate almost doubled the
improvement of his lung function compared to only IAC. This is
highly surprising, since potassium perchlorate as a single
treatment caused no improvement of the lung function at all. In
addition, his cough and sputum production was considerably reduced
compared to when he only took IAC or only iodine, only activated
charcoal, or only perchlorate.
* * * * *