Drug – bio-affecting and body treating compositions – Effervescent or pressurized fluid containing – Organic pressurized fluid
Reexamination Certificate
2001-09-04
2004-03-30
Padmanabhan, Sreeni (Department: 1619)
Drug, bio-affecting and body treating compositions
Effervescent or pressurized fluid containing
Organic pressurized fluid
C514S454000
Reexamination Certificate
active
06713048
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention is generally related to the therapeutic use of &Dgr;
9
Tetrahydrocannabinol (&Dgr;
9
THC). In particular, the invention provides a metered dose inhaler (MDI) for the aerosol administration of &Dgr;
9
THC to patients suffering from nausea and vomiting associated with cancer chemotherapy, muscle spasticity, pain, anorexia associated with AIDS wasting syndrome, epilepsy, glaucoma, bronchial asthma, mood disorders, and the like.
2. Background Description
In 1997, the National Institutes of Health (NIH) released a review of the scientific data concerning potential therapeutic uses for marijuana. In that review, the NIH found that marijuana may indeed have beneficial medicinal effects and recommended that researchers develop alternative dosage forms for the drug, such as a “smoke free” inhaled delivery system. Workshop on the medical utility of marijuana, National Institutes of Health, August 1997. Studies have documented therapeutically beneficial medicinal uses of the major active component of marijuana, &Dgr;
9
tetrahydrocannabinol (&Dgr;
9
THC). Beal, J. A., Olson, R., Lefkowitz, L., Laubenstein, L., Bellman, P., Yangco, B., Morales, J. O., Murphy, R., Powderly, W., Plasse,.T. F., Mosdell, K. W. and Shepard, K. W., Long-term efficacy and safety of dronabinol for acquired immnunodeficiency syndrome-associated anorexia,
J Pain. Symptom Manage
. 14:7-14 (1997); Beal, J. A., Olson, R., Laubenstein, L., Morales, J. O., Beliman, B., Yangco, B., Lefkowitz, L., Plasse, T. F. and Shepard, K. V. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS,
J Pain. Symptom Manage
,. 10:89-97 (1995); McCabe, M., Smith, F. P., MacDonald, J. S., Wooley, P. V., Goldberg, D. and Schein, P. S., Efficacy of tetrahydrocannabinol in patients refractory to standard antiemetic therapy,
Invest. New Drugs
6:243-246 (1988); Lucas, V. S. and Laszlo, J. &Dgr;
9
-THC for refractory vomiting induced by cancer chemotherapy,
JAMA
243:1241-1243 (1980); Sallan, S. E., Cronin, C., Zelen, M. and Zinberg, N. E., Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of &Dgr;
9
THC and prochlorperazine,
N. Engl. J Med
., 302:135-138 (1980); Frytak, S., Moertel, C. G., O'Fallon, J R., Rubin, J., Creagan, E.T., O'Connell, M. J., Schutt, A. J. and Schwartau, N. W., Delta-9-tetrahydrocannabinol as an antiemetic for patients receiving cancer chemotherapy: a comparison with prochlorperazine and a placebo,
Ann. Inter. Med
91:825-830 (1979); Chang, A. E., Shiling, D. J., Stillman, R. C., Goldgerg, N. H., Seipp, C.A., Barofdky, I., Simon, R. M. and Rosenberg S A, &Dgr;
9
THC as an antiemitic in cancer patients receiving high-dose methotrexate.
Ann. Internal Med
. 91:819-824 (1979); Sallan, S. E., Zinberg, N. E. and Frei, I.E., Antiemetic effect of &Dgr;
9
THC in patients receiving cancer chemotherapy,
New Engl. J Med
. 293:795-797 (1975); Noyes, J R., Brunk, S. F., Baram, D. A. and Canter, A., The analgesic properties of &Dgr;
9
THC and codeine.
J Clin. Pharmacol
15:139-143 (1975); Noyes, R., Jr., Brunk, S. F., Baram, D. A. and Canter, A., Analgesic effect of &Dgr;
9
tetrahydrocannabinol,
Clin. Pharmacol & Ther
18:84-89 (1975); Brenneisen, R., Egli, A., Elosohlly, M. A., Henn, V. and Spiess, Y., The effect of orally and rectally administered &Dgr;
9
THC on spasticity: a pilot study with 2 patients,
Int. J Clin. J Pharmocol Ther
. 34:446-452 (1996); Ungerleider, J. T., Andyrsiak, T. F. L., Ellison, G. W. and Myers, L. W., &Dgr;
9
THC in the treatment of spasticity associated with multiple sclerosis,
Adv. Alcohol Subst. Abuse
7:39-50 (1987); Clifford, D. B., Tetra-hydrocannabinol for tremor in multiple sclerosis,
Ann. Neurol
13:669-171 (1983); Petro, D. J. and Ellenberger, C., Treatment of human spasticity with delta 9 -tetrahydrocannabinol,
J Clin. Pharmacol
21:413S-416S (1981); Maurer, M., Henn, V., Dittrich, A. and Hofman, A., Delta 9-tetrahydrocannabinol shows antispastic and analgesic effects in a single case double-blind trial,
Eur. Arch. Psychiatry Neurol Sci
. 240:1-4 (1990); Merritt, J., Crawford, W., Alexander, P., Anduze, A. and Gelbart, S., Effects of marijuana on intra ocular and blood pressure in glaucoma, Opht. 87:222-228 (1980); Cooler, P. and Gregg, J. M., Effect of delta 9-&Dgr;
9
THC on intra ocular pressure in humans.
South. Med J
70:951-954 (1977). Table 1 summarizes the findings of these studies.
TABLE 1
The Use of &Dgr;
9
THC for the Treatment of Assorted Clinical Conditions
Condition and
Administration
Number of Patients
Route and Dose
Findings
Reference
AIDS-associated anorexia
Oral placebo, 2.5 mg
Long term THC treatment
Beal et al., 1997
and cachexia;
THC once or twice
was well-tolerated; THC
94 patients;
daily increasing to 20
improved appetite and only
12 months
mg daily
tended to increase weight
compared to controls
AIDS-associated anorexia
Oral placebo or 2.5
57% and 69% of vehicle
Beal et al., 1995
and cachexia;
mg THC twice daily
and THC patients were
139 patients;
evaluable for efficacy.
42 days
Appetite increased 38%
over baseline for THC
group compared to only
8% for the placebo group.
THC also decreased
nausea. No significant
changes were found
between the groups for
weight change.
Nausea and emesis due to
Oral THC, 15 mg/m
2
Reduction in
McCabe et al., 1988
Cancer chemotherapy;
chemotherapy-induced
36 patients who had
nausea and vomiting in
experienced severe
64% of patients given THC
nausea and vomiting that
compared to
was refractory to
prochloperazine; side
prochlorperazine or
effects included dysphoria;
thiethylperazine
authors recommend initial
THC dose of 5 mg/m
2
Nausea and emesis due to
Oral 5 or 15 mg/m
2
72% of patients exhibited a
Lucas and Laszlo,
Cancer chemotherapy;
THC four times per
THC-induced partial or
1980
53 patients which were
day
complete blockade of
refractory to other
vomiting
antiemetics
Nausea and emesis due to
Oral 10 mg/m
2
THC
THC more effective than
Sallan et al., 1980
cancer chemotherapy;
of prochloperazine
prochloperazine
84 patients
Nausea and emesis due to
Oral 15 mg THC,
Equal antiemetic effects
Frytak et al., 1979
Cancer chemotherapy;
10 mg prochloperzine
between THC and
116 patients
or placebo
prochlorperazine, effects of
each greater than placebo;
considerately more CNS
side effects with THC than
prochlorperazine
Nausea and emesis due to
Oral placebo or 10
93% patients had a
Chang et al., 1979
Cancer chemotherapy;
mg/m
2
THC every 3
reduction in nausea and
15 patients
hours for a total of 5
vomiting, 53% had an
doses, THC (17 mg)
excellent response, 40%
laced cigarettes of
had a fair response; plasma
placebo were given if
THC levels 7.1 ± 6.9 (mean
vomiting occurred
+ SD) ng/ml. Side effects
tachycardia, few other side
effects
Pain due to advanced
Oral placebo and 5,
Pain relief, elevated mood,
Noyes, et al., 1975
cancer; 10 patients
10, 15 or 20 mg THC
appetite stimulation,
drowsiness, slurred speech,
mental clouding
Pain due to advanced
Placebo, 10 and 20
THC produced a similar
Noyes et al., 1975
cancer; 34 patients
mg THC, and 60 and
degree of analgesia, with
120 codeine
greater potency than
codeine. THC CNS side
effects included sedation,
mental clouding, ataxia,
and disorientation
Spasticity related to
Oral 10 or 15 mg
Improvement in passive
Brenneisen et al.,
multiple sclerosis; 2
THC, rectal dose of 5
mobility and walking
1996
patients
or 10 mg THC
ability
Spasticity related to
Oral 2.5 to 15 mg
Significant subjective
Ungerleider et al.,
multiple sclerosis; 13
THC once or twice
improvement in spasticity
1987
patients
daily or placebo
at 7.5 mg THC and higher,
no significant improvement
in objective measurements
Spasticity related to
Oral 5 to 15 mg THC
5 of 8 patients had mild
Clifford, 1983
multiple sclerosis; 8
subjective improvement in
patients, single blind
tremor. 2 of 8 patients had
both objective and
subjective improvement
Spasticity related to
Placebo, or 5 or 10
Decrease in spasticity
Petro and
multiple sclerosis; 9
mg THC
compared to placebo
Ellenbe
Byron Peter R.
Lichtman Aron H.
Martin Billy R.
Peart Joanne
Padmanabhan Sreeni
Virginia Commonwealth University
Wells Lauren Q.
Whitham Curtis & Christofferson, P.C.
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