CD4+
Lymphocyte
Level
in
HIV Patients
Trioxolane
vs.
Clinical Complaints
Trioxolane
vs. CD4+
Lymphocytes in
HIV Patients
Blood
Sample
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Clinical
Trials
Particulars
of clinical tests conducted with reference to the efficacy of
the use of the drug with a summary of the nature of the tests,
by whom conducted and where, results etc., and with special
reference to comparative or controlled clinical test, double
blind tests, etc.
1.
Systemic Infections
2.1
HIV/AIDS
A
minimum of 25 patients have been followed in Kenya and in
the United States over a period of from 2 to 4 years on a
dosage regimen of approximately 200 milligrams daily. All
patients have shown improvement and stabilization of both
clinical and laboratory parameters of disease (refer also
to Paragraph 9 for more information).
4
patients have been treated over a period of from 3 to 4 years.
These include one Adenocarcinoma of the Lung, one Hodgkin's
disease, and two non-Hodgkin's Lymphomas. Patients were treated
on a daily dose basis of 200 milligrams daily. In all patients,
during the course of treatment, there was regression of tumor
or cessation of growth of tumor, as well as improvement in clinical
parameters. One patient demonstrated reinstitution of tumor
growth with forced cessation of therapy. The other patients
remain in remission.
8
patients with long-standing active RA were placed, on a dose
of 200 milligrams daily. All patients had evidence of remission
of symptoms within 2 weeks, and in all patients, all evidence
of active disease had cleared within 6-8weeks. Patients have
remained asymptomatic with no evidence of progression of disease
for two years.
2.4 OSTEOARTHRITIS
AND IMFLAMMATORY POLYARTHRITIS
15
patients, including those with degenerative, psoriatic and
arthritis associated with chronic fatigue syndrome, as well
as non-specific polyarthritis were studied. These patients
were treated with a daily do of 200 milligrams. All patients
showed substantial or complete disappearance of all symptoms
within 8 weeks. All patients have been maintained without
symptoms and without evidence of progression of disease.
2.5 CHRONIC
FATIGUE SYNDROME
4
patients were treated with 200 milligrams daily. All patients
showed marked improvement. All symptoms were completely or
substantially disease cleared within 3 months.
1
patient with associated colitis and arthritis. All signs and
symptoms of active disease cleared within 90 days with compete
resolution of arthritis, colitis and reduction of ANAtiter
from 1:1880 down to 1:30.
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2.
Topical Diseases
3.1.
FUNGAL DISEASES OF THE SKIN:
30
patients were treated for various forms of skin fungus unresponsive
to other forms of therapy. All patients had complete clearing
of skin lesions within 4-6 weeks. The lesions were treated with
a 3% solution of active ingredient with propylene glycolonce
twice daily.
3.2.
BACTERIALDISEASES OF THE SKIN:
In a series of 40 patients with chronic acne vulgaris of varying
degrees of severity, a 3% solution was applied to the lesions
on a daily basis. Al lpatients showed significant or marked
clearing of lesions New lesions formed less often and cleared
quickl with subsequent applications.
3
patients had complete clearing within 1 week with application
of 3% solution twice daily.
4
patients. Lesions cleared rapidly and completely in all cases
with 48 hours of beginning application of 3% solution.
3.2.4WOUNDHEALINGand
SCARPREVENTION:
Various
surgical and non-surgical wounds were treated with a 3% solution
on a daily basis. Wounds so treated were shown to heal faster,
with no evidence of secondary infection and noticeable reduction
in scar formation: Those persons prone to keloid formation
had no evidence of keloid formation withthe use of this treatment.
3.3
VIRAL DISEASES OF THE SKIN
40
patients comprising Herpes simplex, genitalis, zoster, and
ophthalmic were treated with a topical solution of 3% active
ingredient in oroovlene alvcoL and in the case of oohthalmic
with afresh 112% solution in saline with a small amount
of propylene glycoll as solubilizing agent. In all herpes
genitalis and simplex cases, all lesions when treated early,
showed rapid cessation of viral expression and rapid clearing
of lesions in most cases, without evidence of blister formation.
Most lesions cleared completely within 48 hours. Lesions,
which had progressed to significant size prior to treatment,
required 3-4 days for complete resolution. Herpes zoster
(5 cases), all cases showed slow progressive resolution
of lesions, with complete clearing in approximately2-6 weeks.
Most lesions had been present for up over 6 months. Ophthalmic
herpes (2 cases), in both cases lesions showed definit early
clearing, with resolution in one case within48 hours and
the other case in 4 days.
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3.3.2
VENEREAL WARTS:
4
patients. A solution of 3% active ingredient in propylene
glycol was applied 3 times daily with complete clearing
of all lesions in 2 weeks.
3.3.3
COMMON WARTS (MULTIPLE MANIFESTATIONS):
26 patients. 10% solution was applied 2 times daily. All
patients showed resolution with treatment; however, there
was marked variation in time to complete clearing, depending
apparently upon the type of presentation of the wart. Some
warts cleared within 2 weeks, while most required several
months and a few
3.4. DERMATOLOGICAL
14
patients. Various forms of eczema or neuro-dermatitis
were treated and approximately 112showed complete resolution
of lesions within6 weeks. Approximately 30% sowed significant
improvement and the remainder showed only slight or no
improvement.
3.4.2 PSORIASIS:
13
patients. Agroup of patients with various degrees of severity
were treated. Milder cases were treated with topical application
of 3% solution and there was marked or complete resolution
of lesions in all but 2 cases. 3 cases of severe generalized
dermatitis were treated with a combination of 3% topical
once or twice dailyor with systemic dosage of 200 milligrams
3 times weekly. All showed complete clearing of lesions
within 6 weeks.
3.4.3 INSECT BITES:
Multiple
cases of insect bites, including those of mosquito, bee,
wasp, fly, flea, totaling in excess of20 patients were
treated. All lesions showed almost immediate relief of
pain, itching, with rapid reduction of swelling and erythema.
All lesions cleared completely within 24 to 48 hours.
3.4.4
CORAL BURNS I JELLYFISH STINGS:
18
patients. All pain, swelling and erytherna was alleviated
rapidly with either complete clearing or minor residual
erythema within 24 ours.
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3.4.5
POISON OAK:
3
patients. Application of 3% solution provided marked and
immediate relief of itching and in 2 cases with complete
clearing of lesions within 48 hours.
3.4.6 SEBORRHEIC DERMATITIS:
10
patients. lesions involving the scalp and eyebrows were
treated with once daily applications with marked response
and reduction of lesions in 9 out of 10 cases.
3.4.7
BURNS:
19
patients with first and second-degree burns. Most patients
reported immediate and substantial or complete relief
of pain. Most patients showed evidence of the development
of bulla and there was rapid and substantial reduction
in swelling and erythema in all patients. Nothird degree
burns were treated.
3.
Arlhritis
4.1.ARTHRITIS:
5
patients of relatively severe arthritis of small joints were
treated with 6% topical applications twice daily. All patients
reported marked or complete relief of pain within 2 weeks.
4.
Dental and Oral Conditions
5.1.
PHARYNGITIS:
17
patients with varying degrees of tonsillitis or pharyngitis
were treated with topical application of3% active ingredient
in glycerin 4 times each day. All patients showed moderate
to rapid relief of pain with reduction of swelling in the
first 24 hours. Complete resolution
5.2.
TOOTH ACHE:
7
patients with varying degrees of dental pain from tooth ache
experienced immediate and substantial relief from pain with
application of 3% topica lsolution to the surrounding gums.
5.3.
GINGIVITIS:
3
patients with gingivitis had a marked or complete resolution
within 3 months upon using 3-4 drops 3% Geraniol trioxolane
in glycerin with toothpaste.
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5.
Oral Manifestations of Bacterial
6.1.
HALITOSIS:
10
patients with chronic halitosis all reported marked or complete
resolution of the halitosis with daily use offour drops of 3%
solution in glycerin during brushing of teeth.
6.2. CANKER SORES:
9
patients. All patients reported rapid resolution of pain and
discomfort with complete clearing of lesions within 24 to 48
hours b application of 3% solution 3 times a day. Overgrowth
A
pilot study using 4 couples using a vaginal suppository of 1.5%
solution in high molecular weight polyethylene glycol (Plurocols)
over a 4 month program and there has been no evidence of conception
to date.
7.2.
HEMORRHOIDS:
21
patients with hemorrhoids ranging from small external symptomatichemorrhoids
to large external and internal bleeding hemorrhoids were put
on treatment. All cases showed substantial 0 complete resolution
within 1week using 3%topical solution or a combination of topical
and rectal suppository.
7.
Microcapillmy Blood Circulation
Routine
examination of wet freshly drawn whole blood from 40 clinically
normal individuals indicates a general cellular stickiness
with massive red cell agglutination, irregular cell size and
shape, and extraneous intracellular debris that includes pleomorphic
granules, especially in the extremities. We believe that this
manifestation usually accounts for poor tissue and organ oxygenation
leading to poor blood circulation and tissue functioninthese
sites. However,when the product is administered as prescribed,
and blood drawn in about 20 minutes and examined, marked and
obvious changes are seen. Within 20 minutes, the red cells
have plumped up and show more homogenous size and shape. They
have "lost" the previously seen "stickiness" and now appear
less viscous and "teflonized" and move much more freely without
any evidence of agglutination. Capillary perfusion is now
markedly improved. This observation, alone, makes the product
potentially useful in the prevention and management of stroke
and heart attack, and in the prevention of debilitating complications
associated with
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8.
Clinical Trials on HIV/AIDS
Previous
clinical and experimental studies explained earlier were primarily
meant to test the clinical safety and efficacy of KE091JATX
on infections whose causative agents have been tested in vitro,
and on ot clinical conditions where its potential use is likely
to be indicated. of KE091JATX for various clinical conditions.
Attempts
have been made to work out formulations, dosages, stability
anI routes of administration clinical trial protocol was designed
to test the efficacy of KE091JATX in' clinical management of
opportunistic infections and other symptoms associated with
HIV infections and AIDS.
9.3.
Observations
9.3.1. 80th
laboratory and clinical observations are summarized in Table
9. and Table 9.2 and Graph 1. Major clinical complaints
were fatigue, weakness, difficulty in swallowing, loss of
appetite, nausea, vomitin diarrhea, weight loss, fever,
night sweats, headache, and cough. Other complaints included
insomnia, impaired concentration, paraesthesi: and pruritis.
Fatigue or weakness, loss of appetite and difficulty in
swallowing were the most common complaints and fatigue,
weaknes,s diarrhea and headaches usually persisted and were
last to resolve.
9.3.2.
As indicated, those patients on KE091JATX (oropharyngeal
and suppository) clearly benefited as opposed to those on
placebo (controls). addition, those on oropharyngeal preparation
responded better than those on suppositories. The reason
here is that a number of patients on suppositories complained
of occasional anal irritation and recurrence of diarrhea.
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From
the data obtained so far, it is clear that different formulations
of the product are effective against an extremely wide spectrum
of bacteria, fungi, viruses and protozoa. They have also been
observed to be spermicidal, as well as immunomodulatory. There
is no recognized toxicity or undesirable side effect associated
with their use. These products are therefore believed to be
potent drugs for use in a very wide range of activities.
80th
Geraniol trioxolane and the trioxolane derivative of cis 3-
hexene-1-ol are potentially active compounds against a variety
of organisms, notable ones being protozoa (Leishmania spp.),
both gram positive and gram negative bacteria, and fungi. An
additional activity observed in vitro is their ability to kill
spermatozoa and cultured mveloma cells. On results from ongoing
studies on safetv and toxicitv, the products are believed to
be safe for human use as drugs.
In
addition to the clinical data obtained on Geraniol trioxolane
and the trioxolane derivative of cis 3-hexene..1-01,we have
obtained clinical data using erucic acid ozonated in accordance
with the method of Example 1. This ozonated compound is active
in vitro against a wide variety of bacterial and fungal pathogens.
The compound has successfully been used topically in a propylene
glycol base at 2% active material to treat genital and oral
herpes, fungal infections, wasp stings, eczema, and diaper rash.
In addition, a three-month trial on three ARC(AIDSRelated Complex)
patients and one lymphoma patient, remission of disease was
maintained after an initialtreatment with Geraniol trioxolane
resulted in remission.
The
trioxolane and diperoxide derivatives of both terpene and nonterpene
unsaturated hydrocarbons are all believed to have the same mechanism
of action. Whilenot wishing to be bound by any particular mode
of action, it is believed that these compounds release pharmacologically
active zwitterion moieties upon hydrolysis. In view of the compound's
perceived common mechanism of action, it is believed that a
wide variety of diperoxide and trioxolane derivatives of terpene
and non-terpene unsaturated hydrocarbons have activities similarto
the activities reported in this section for Geraniol trioxolane
and the trioxolane derivative of cis-3..hexene-1-01.
These
reports and observations (published and/or unpublished, and
which cover a period of more than ten years) were made by:
Dr.
Stephen D. Herman, USA
Drlack
H. Haddad, Professor and Director, Allergy/Immunology, USC,USA
Dr lIIianaGonzalez, Center for Pharmaceutical Chemistry,
Mexico
Dr Carmen L. Garcia, Center for Research and Development
of Medicines (CIDEM),Mexico
Dr Celia Llerna and DrVivianaBueno, CIDEM,Mexico
DrJuana I. Tillan Capo, Chief of Biological Control Laboratory,
CIDEM(an ISO10993certified laboratory)
Dr DavyKoech, KEMRI Dr KofiM.Kofi-Tsekpo, KEMRI
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