U.S. patent application number 10/406869 was filed with the patent office on 2004-03-25 for dri-nasal sprays.
Invention is credited to Mackles, Leonard.
Application Number | 20040057907 10/406869 |
Document ID | / |
Family ID | 36752883 |
Filed Date | 2004-03-25 |
United States Patent
Application |
20040057907 |
Kind Code |
A1 |
Mackles, Leonard |
March 25, 2004 |
Dri-nasal sprays
Abstract
There is provided non-aqueous liquid spray compositions
comprising a pharmacologically acceptable non aqueous liquid
carrier in which said bioactive material is directly insoluble, a
pharmacologically acceptable water insoluble ester of a water
soluble acid soluble in said carrier, a pharmacologically
acceptable water soluble glycol soluble in said ester and a
pharmacologically acceptable water soluble bio-active material
soluble in said glycol but not directly soluble in the carrier.
There are also provided methods of producing and administering such
compositions.
Inventors: |
Mackles, Leonard; (New York
City, NY) |
Correspondence
Address: |
Omri M. BEHR
325 Pierson Ave
Edison
NJ
08837
US
|
Family ID: |
36752883 |
Appl. No.: |
10/406869 |
Filed: |
April 4, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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10406869 |
Apr 4, 2003 |
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10253073 |
Sep 23, 2002 |
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Current U.S.
Class: |
424/45 |
Current CPC
Class: |
A61K 9/0043 20130101;
A61K 47/10 20130101; Y10S 514/958 20130101; A61K 47/14 20130101;
Y10S 514/957 20130101; A61K 47/24 20130101 |
Class at
Publication: |
424/045 |
International
Class: |
A61L 009/04 |
Claims
1. A non-aqueous liquid spray composition for a bioactive material
comprising 1) a pharmacologically acceptable non aqueous liquid
carrier in which said bioactive material is directly insoluble, b)
a pharmacologically acceptable water insoluble ester of a water
soluble acid soluble in said carrier, c) a pharmacologically
acceptable water soluble glycol soluble in said ester, d) a
pharmacologically acceptable water soluble bio-active material
soluble in said glycol but directly insoluble in said carrier.
2. The composition of claim 1 wherein . the carrier is selected
from the group consisting of a cyclopentasiloxane, an ethylene
diglyceride, a propylene diglyceride, a propylene triglyceride and
mixtures of said glycerides.
3. The composition of claim 2 wherein the cyclopentasiloxane is a
polyalkylcyclopentasiloxane.
4. The composition of claim 3 wherein the carrier is selected from
the group consisting of decamethylcyclopentylsiloxane, an ethylene
diglyceride, a propylene diglyceride, a propylene triglyceride and
mixtures of said glycerides, wherein the glyceride moieties are
selected from the group consisting of cAprilic and capric
glycerides.
5. The composition of claim 1 comprising a) from about 50-about 90
wt. % of the carrier, b) from about 1 0-about 40 wt % of the water
insoluble ester, c) from about 1-about 5 wt. % of the water soluble
glycol, d) from about 0-01-about 2 wt. % of the bio-active
material.
6. The composition of claim 1 comprising a) from about 60 about 90
wt. % of the carrier, b) from about 10 about 20 wt % of the water
insoluble ester, c) from about 1 to about 3 wt. % of the water
soluble glycol, d) from about 0.01 to about 2 wt. % of the
bio-active material.
7. The composition of claim 5 wherein the glycol is a C.sub.3 to
C.sub.8 glycol.
8. The composition of claim 7 wherein the glycol is selected from
the group consisting of polyethylene glycol and polypropylene
glycol.
9. The composition of claim 5 wherein the ester is a lactate
ester.
10. The composition of claim 9 wherein the lactate ester is a
C.sub.12- C.sub.15 alkyl lactate
11. The composition of claim 10 wherein the alkyl group is selected
from the group consisting of cetyl, lauryl, isostearyl and myristyl
and mixtures thereof
12. The composition of claim 5 wherein the bio-active material is
selected from the group consisting of decongestants,
antihistamines, antitussives, anticholinergics, steroids,
antibiotics, analgesics, antispasmotics, brocho-dilators, vitamins,
hormones, antihypertensives and antimicrobials.
13. The composition of claim 5 wherein the bio-active material is a
decongestant.
14. The composition of claim 13 wherein the bio-active material is
selected from the group consisting of oxymetazoline,
xylometazoline, naphazoline, phenylephrine, ephedrine in water
soluble form.
15. The composition of claim 14 wherein the bio-active material is
in the form of a pharmacologically acceptable salt.
16. The composition of claim 15 wherein the salt is a hydrochloride
or sulfate.
17. A method of producing a spray composition of claim 1 which
comprises the sequential steps of dissolving the bio-active
material of (d) in a glycol of (c), dissolving said solution of (d)
in (c) in an ester of (b) and dissolving said solution of (d) in
(c)) in (b) in a carrier of (a).
18. The method of producing a spray composition of claim 2 which
comprises the sequential steps of dissolving the bio-active
material of (d) in a glycol of (c), dissolving said solution of (d)
in (c) in an ester of (b) and dissolving said solution of (d) in(c)
) in (b) in a carrier (a) as defined in claim 2.
19. The method of producing a spray composition of claim 5 which
comprises the sequential steps of dissolving the bio-active
material of (d) in a glycol of (c), dissolving said solution of (d)
in (c) in an ester of (b) and dissolving said solution of (d) in
(c) in (b) in a carrier of (a) selected from the group consisting
of decamethylcyclopentylsiloxane, an ethylene diglyceride, a
propylene diglyceride, a propylene triglyceride and mixtures of
said glycerides, wherein the glyceride moieties are selected from
the group consisting of cAprilic and capric glycerides.
20. A method of administering a bio-active material to a subject in
need of same which comprises spraying a pharmacologically effective
amount of a composition of claim 1 into the nasal cavity of said
subject.
21. The method of claim 20, wherein the bio-active material is
selected from the group consisting of decongestants,
antihistamines, antitussives, anticholinergics, steroids,
analgesics antibiotics, antispasmotics, brochodilators, vitamins,
hormones, antihypertensives and antimicrobials.
22. The method of claim 21, wherein the bio-active material is a
decongestant.
23. The method of claim 22, wherein the bio-active material is
selected from the group consisting of oxymetazoline,
xylometazoline, naphazoline, phenylephrine, ephedrine in water
soluble form.
Description
RELATED APPLICATIONS
[0001] This application is a continuation in part of applicants
copending application Ser. No. 10/253,073, filed Sep. 23, 2002.
FIELD OF THE INVENTION
[0002] Safe, non irritating, non aqueous spray compositions
administrable via the nasal cavity.
BACKGROUND OF THE INVENTION
DISCUSSION OF THE PRIOR ART
[0003] The use of nasal sprays to provide relief from the nasal
stuffiness of colds and allergic rhinitis is widespread. Various
sympathomimetic amines have been used to provide relief. Nasal
decongestants stimulate the alpha-adrenergic receptors of the
vascular smooth muscle. This constriction results in shrinkage of
the engorged mucous membranes which promotes drainage; improves
nasal ventilation and relieves the feeling of stuffiness.
[0004] Many decongestants are commercially available and are used
to give various lengths of relief from 4 hours up to 12 hours. All
of these decongestants are water soluble and are delivered in
aqueous spray Systems.
[0005] The decongestant solutions are delivered by spray from
either a flexible plastic container that produces a mist when
squeezed or by a hand operated mechanical pump.
[0006] These aqueous sprays are wet, cold and drip from the nose.
They are very uncomfortable to use. Since they are aqueous based
and the nozzle is inserted in the nostril, bacterial contamination
of the product easily occurs. Nasal sprays are difficult to
preserve.
[0007] The mucous layer lining the epithelium represents a barrier
to drug absorption along with mucociliary clearance mechanisms of
the nose leads to short residence time of aqueous systems at the
site of absorption which limits the systemic availability of the
drug.
SUMMARY OF THE INVENTION
[0008] The invention is directed to compositions of incorporating
an effective dosage of decongestant or other drug from a safe,
non-aqueous, non-irritating, tastless and odorless liquid carrier
system that delivers an extremely fine, non-dripping, warm,
pleasant spray to the nasal cavity from either a squeeze bottle or
pump spray system.
[0009] There is provided a non-aqueous liquid spray composition for
a bioactive material comprising a pharmacologically acceptable non
aqueous liquid carrier in which said bioactive material is directly
insoluble, a pharmacologically acceptable water insoluble ester of
a water soluble acid soluble in said carrier, a pharmacologically
acceptable water soluble glycol soluble in said ester, a
pharmacologically acceptable water soluble bio-active material
soluble in said glycol but directly insoluble, that is to say
cannot be directly dissolved in in said carrier.
[0010] The spray compositions of the present invention are produced
by the sequential steps of dissolving the bio-active material in a
glycol, dissolving the resultant solution in a water insoluble
ester of a water soluble acid and dissolving said further resultant
solution in a suitable carrier as discussed above.
[0011] The spray compositions of the present invention containing
the appropriate bio-active material may be administered to a
subject in need of same by spraying a pharmacologically effective
amount of such a composition into the nasal cavity of said subject.
This may be done using any spray method, such as using a pump spray
device or a squeeze bottle spray, the latter being inexpensive and
especially suitable.
[0012] The system of the present invention possesses several
advantages over the aqueous nasal administration systems heretofore
available. It provides a fine, warm, dripless, non-irritating
spray, which, depending on the drug used, gives 4-12 hour
decongestant relief. Because the system is non-aqueous, no
preservatives are needed and the system will resist
recontamination.
[0013] Furthermore because the system is anhydrous, it will wet out
and cling to the mucous membrane of the nasal passages. Being water
resistant, it will resist removal by the mucocillary clearance
mechanism; thereby allowing more contact time at the site. The
drugs will partition from the system and be adsorbed by the mucosa
giving faster onset of action and greater symptom relief.
[0014] The system works exceptionally well with all commercially
available spray systems. In fact, the efficacy of squeeze bottle
system is comparable to the more expensive pump spray delivery.
[0015] All ingredients are safe for use in the nose. The esters and
glycols used manifest a moisturizing effect which will keep the
nasal tissues soft and supple thereby eliminating nasal dryness. In
addition to the bio-active materials to be administered, the spray
compositions may also include conventional additives such as
essential oils, fragrances, flavors, sweeteners, menthol,
pepperment oil, pine tar, camphor, benzoin preparations, tolu,
turpentine oil and the like.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0016] Suitably the carrier is a cyclopentasiloxane, preferably a
polyalkylcyclopentasiloxxane an ethylene diglyceride, a propylene
glyceride, and mixtures of said glycerides. It especially desirable
that the carrier is decamethylcyclopentasiloxane, an ethylene
diglyceride, a propylene diglyceride, a propylene triglyceride and
mixtures of said glycerides, wherein the glyceride moieties are
selected from the group consisting of caprilic and capric
glycerides.
[0017] Suitably the ester is a lactate ester, desirably it is a
C.sub.12 to C.sub.18 alkyl lactate, preferably where the alkyl
group is cetyl, lauryl, isostearyl and myristyl and mixtures
thereof.
[0018] Preferably, the glycol is a C.sub.3 to C.sub.8 glycol,
including but not limited to propylene, dipropylene, hexylene,
1,3-butylene, diethylene, triethylene, tetrapropylene and
tetraethylene glycols, polyethylene glycol 200 and polypropylene
glycol 425 amd 2-methyl-1,3-propane diol and mixtures thereof
[0019] While the invention is not limited thereto, bio-active
materials suitable for use in this invention include those selected
from the group consisting of decongestants, antihistamines,
analgesics such as butorphanol tartrateantitussives,
anticholinergics, steroids, suitably corticosteroids such as
triamcinolone acetonide antibiotics antispasmotics, such as
beclamethasone dipropionate, brochodilators, such as ipratropium
bromide, fluticasone pripionate, albuterol sulfate, vitamins, such
as vitamine B-12 or cyanocobalamine, hormones, suitably peptide
hormones such as calcitonin-salmon, antihypertensives such as
propranolol, and antimicrobials.
[0020] Especially suitable for purposes of this invention as the
bio-active material are decongestants. Most suitably oxymetazoline,
xylometazoline, naphazoline, phenylephrine, ephedrine in water
soluble form especially when in the form of a pharmacologically
acceptable salt, such as a hydrochloride or sulfate.
[0021] The ranges of the components of the spray composition are
suitably from about 50-about 90 wt. % of the carrier, from about
10-about 40 wt % of the water insoluble ester, from about 1 to
about 5 wt. % of the water soluble glycol, and from about 0.01 to
about 2 wt. % of the bio-active material, to a total wt % of 100.
Preferably the ranges are from about 60 about 90 wt. % of the
carrier, from about 10 about 30 wt % of the water insoluble ester,
from about 1 to about 3 wt. % of the water soluble glycol and from
about 0.01 to about 2 wt. % of the bio-active material.
[0022] The sprays of the present invention are administered by
spraying into the nasal cavity. The actual volume sprayed may lie
between about 20 and about 80 micro liters. This amount is readily
set by those skilled in the art of valve design for squeeze bottles
and spray bottles. Thus the dosage of bio-active delivered is
determined by its concentration in the composition. The needed
frequency of administration may be readily determined by those
skilled in the art based on present knowledge and not requiring
undue experimentation.
EXAMPLES
[0023] (All quantities are in wt. % unless otherwise noted)
Example #1 Nasal Decongestant 12 Hour Duration
[0024]
1 1. Oxymetazoline.HCl 0.05 2. Propylene Glycol 2.50 3.
C.sub.12--C.sub.15 Alkyl Lactate 20.00 4.
Dimethylcyclopentasiloxane 77.45 100.00
[0025] Components # 1 and #2 are heated to 50.degree. C. until
clear and uniform then the batch is cooled the #3 is added with
mixing and when clear, #4 is added and mixed. The batch may then be
charged to a spray container in suitable quantities.
Example #2 Nasal Decongestant 8 Hour Duration
[0026]
2 1. Xylometazoline.HCl 0.10 2. Propylene Glycol 2.50 3.
C.sub.12--C.sub.15 Alkyl Lactate 20.00 4. Cyclopentasiloxane 77.40
100.00
[0027] This mixture is prepared in accordance with the procedures
of Example #1
Example #3 Nasal Decongestant 4 Hour Duration
[0028]
3 1. Phenylephrine.HCl 0.50 2. Propylene Glycol 5.00 3.
C.sub.12--C.sub.15 Alkyl Lactate 30.00 4. Cyclopentasiloxane 64.50
100.00
[0029] This mixture is prepared in accordance with the procedures
of Example #1
Example #4 Nasal Decongestant 12 Hour Duration
[0030]
4 1. Oxymetazoline.HCl 0.05 2. 1,3-Butylene Glycol 2.50 3. Lauryl
Lactate 20.00 4. Cyclopentasiloxane 77.45 100.00
[0031] This mixture is prepared in accordance with the procedures
of Example #1
Example #5 Nasal Decongestant and Antihistamine
[0032]
5 1. Oxymetazoline.HCl 0.05 2. Chlorpheniramine Maleate 0.20 3.
Propylene Glycol 2.50 4. Myristyl Lactate 20.00 5.
Cyclopentasiloxane 77.25 100.00
[0033] Components # 1, #2 and #3 are heated to 50.degree. C. until
clear and uniform then the batch is cooled the #4 is added with
mixing and when clear, #5 is added and mixed. The batch may then be
charged to a spray container in suitable quantities.
Example #6 Nasal Decongestant
[0034]
6 1. Oxymetazoline.HCl 0.05 2. Propylene Glycol 2.00 3. Isostearyl
Lactate 23.00 4. Cyclopentasiloxane 74.95 100.00
[0035] This mixture is prepared in accordance with the procedures
of Example #1
Example #7 Nasal Decongestant 12 Hour Duration
[0036]
7 1. Oxymetazoline HCl 0.05% 2. Propylene Glycol 1.50% 3.
C.sub.12--C.sub.15 Alkyl Lactate 20.00% 4. Caprylic/Capric
Triglyceride 78.45% 100.00%
[0037] This mixture is prepared in accordance with the procedures
of Example #1.
Example #8 12 Hour Duration Nasal Decongestant
[0038]
8 1. Oxymetazoline HCl 0.05% 2. Propylene Glycol 1.50% 3.
C.sub.12--C.sub.15 Alkyl Lactate 10.00% 4. Propylene Glycol
Dicaprylate/Dicaprate 88.45% 100.00%
[0039] This mixture is prepared in accordance with the procedures
of Example #1.
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