Note: Descriptions are shown in the official language in which they were submitted.
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This invention relates to antiseptic spermicidal
compositions, and more particularly to antiseptic
spermicidal compositions for vaginal application, to
protect against transmission of sexually transmitted
viruses and other infections, and to protect against
conception. It also relates to means for effective applica-
tion of such compositions.
Transmission of infection from body to body as
a result of sexual intercourse is one of the principal ways
in which viruses such as herpes 1 and 2, HIV, cytomegalo-
virus, hepatitis B and the like, and venereal bacterial
diseases such as gonorrhea, chancroid, streptococcus,
staphylococcus, gardnerella, mycobacteria, etc are spread.
Particularly at risk from such infection transmissions are
highly sexually active females, e.g. those engaged in the
sex trade, who at the same time run high risks of unwanted
pregnancy. To date, the most commonly recommended form of
protection against such risks has been the use of latex
condoms, optionally in conjunction with a spermicidal
lubricant. This however depends upon co-operation of the
male partner, and does not provide the female participant
with full control over the risks to her own body.
Of particular concern in this regard are condi-
tions in emerging, third-world countries, where the avail-
ability condoms and spermicidal or germicidal compositions
for use therewith is very restricted. The spread of infec-
tious disease, and population control, are items of
especial concern. The problems are complicated by the
relative lack of expert medical facilities in many such
countries, and the educational level of the population at
risk.
Any antiviral and contraceptive system having a
chance of being accepted, widely used and effective in such
places must therefore be simple to use, by the woman
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herself, without expert medical assistance. It should be
capable of being applied well in advance of the time when
the sexual activity is to take place and to remain effec-
tive for a substantial period of time thereafter. Moreover
it should be physically and aesthetically pleasant, so that
it does not detract unnecessarily from the sexual activity.
It is an object of the present invention to
provide a novel spermicidally effective and virucidally
effective composition for female use.
It is a further object of the invention to
provide a kit and method for use of such a composition.
SUMMARY OF THE INVENTION
The present invention provides a clear gel
formulation for vaginal application, which is contracep-
tively effective as a spermicide, and antivirally effective
to prevent HIV transmission. A formulation has been found
which can be applied to the vaginal walls, and will remain
thereon in quantities or concentrations to confer effective
protection against HIV reception by the female for at least
24 hours following application, without exhibiting harmful
effects to these very sensitive mucous-bearing skin sur-
faces. The formulation contains a very small amount of a
strong disinfectant namely one or more benzalkonium chlor-
ides, and a spermicidal substance such as an octoxynol-9,
a nonoxynol, and/or triclosan, along with sodium carbomer
and other inert ingredients carefully chosen as to both
nature and quantity so as to provide a clear semi-solid gel
capable of remaining on the vaginal walls for at least 24
hours after application, in a virucidally effective form.
Thus, according to the present invention, from
one aspect, there is provided a spermicidally and
virucidally effective, vaginally applicable formulation,
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having the following approximate composition of essential
ingredients:
at least one benzalkonium chloride, in an amount
from 0.05 to 0.2~;
at least one spermicide selected from the group
consisting of nonoxynols in an amount of from 0.05-12~,
octoxynol-9 in an amount of from 0.05-4~, and 5-chloro-2-
(2,4-dichlorophenoxy)phenol in an amount from 0.05-2~;
a biologically acceptable emollient, providing
appropriate consistencyi
hydroxypropylmethyl cellulose, in an amount from
0.1-3~;
sodium carbomer, in an amount from 0.1-1~;
de-ionized water, making up the balance, the
formulation further possessing the attributes of (a) a
semi-solid, essentially clear gel consistency and appear-
ance, and (b) the ability to maintain a presence in the
human vagina along with mucous secretions therein, in
virucidally effective amounts, for at least 24 hours after
application thereto.
Another aspect of the present invention provides
a kit for vaginal self-use by a female patient in protec-
tion against contracting viral infection and against
conception as a result of normal heterosexual intercourse,
said kit comprising a vaginal applicator comprising a
vaginally insertable tubular member having a length of
about five inches, and having an aperturable distal end
adapted to be positioned adjacent to the patient's cervix
when the applicator is fully inserted into the patient's
vagina, and at least one unit dose of the spermicidally and
virucidally effective formulation described above, said
unit dose being from about 5-10 mls thereof.
In the accompanying drawings:
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FIGURE 1 is a side view of an applicator for use
in the kit of the present invention;
FIGURE 2 is a cross sectional view of the appli-
cator of Fig. 1, along the line 1-1 of Fig. 1.
The benzalkonium chlorides used in the present
invention are known compounds, many of which have previous-
ly been sold and used for disinfecting purposes in non-skin
contacting applications. Thus, they are sold for purposes
of making up a disinfectant wash solutions for floors,
walls, operating surfaces and the like, but always with
strong warnings to avoid skin contact with them if at all
possible. They are powerful poisons and skin irritants, as
well as powerful disinfectants. The present invention takes
advantage of the fact, hitherto unreported, that they will
destroy harmful viruses such as herpes simplex types 1 and
2 and HIV when they are present in formulations in such low
concentrations that they acceptable on and non-harmful to
the human vaginal walls. These viruses in fact are not
difficult to kill when encountered in isolation in external
body fluids or secretions. It is after they have infected
the m~mm~l ian body and become to replicate in the body
cells that they become almost impossible to treat effec-
tively. If the viruses can be caught and treated on
transmission from body to body, they are w lnerable to
common disinfectants such as those used in the compositions
of the present invention.
To safeguard against risks of skin irritation,
the benzalkonium chloride is preferably used in the compo-
sition of the present invention in amounts from 0.05-0.12~
by weight. Specific examples of benzalkonium chlorides for
use in the present invention include alkyl dimethyl benzyl
ammonium chloride and alkyl dimethylethylbenzyl ammonium
chloride, in which the alkyl portions are C12-C18 in length,
and mixtures thereof, and myristylbenzalkonium chloride.
213~68~
Such a suitable mixture is available commercially under the
trade name MAQUAT MQ2525M - 50~, from Mason Chemical
Company, Chicago, Illinois, and under the trade name BTC
2125M from Stepan Company, North Field, Illinois.
Compositions according to the present invention
also include a small but effective amount of a spermicide.
The spermicide is selected from nonoxynols, octoxynol-9 and
triclosan [which is, chemically, 5-chloro-2-(2,4-dichloro-
phenoxy)phenol)], and are used in the amounts set out
above. The octoxynol series are polyethylene glycol p-
isooctylphenyl ethers such as octoxynol-9 (Triton X - 100).
The nonoxynol series are polyoxyethylene nonylphenyl
ethers, of various numbers of ethylene oxide units, e.g. -
nonoxynol 9 and nonoxynol 10. They also confer surfactant
properties on the compositions of the invention, making
them easier to spread over the surface of the vaginal
walls.
Whilst the various additional ingredients added
to the composition of the present invention are in a sense
carriers, in that they are not virucidally or spermicidally
active, they nevertheless play important roles in determin-
ing the nature and thereby rendering the compositions
acceptable for use. The combination of the emollient
(which is preferably glycerine), sodium carbomer and
hydroxypropylmethyl cellulose in the specified relative
amounts in the formulation of the invention ensures a semi-
solid clear gel composition, which is a very important
factor in the acceptability of the composition for its
intended use. Opaque, coloured compositions will not gain
consumer acceptance for vaginal use as a protectant against
sexually transmitted infections.
Even more important is the fact that the composi-
tion of the invention has its inert ingredients selected
and present in amounts which ensure a gel which is long
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lasting in its effectiveness after application. The combi-
nation of the hydroxypropylmethyl cellulose and the sodium
carbomer in the specified proportions ensures a composition
of sufficient adherence to the patients' vaginal walls that
it remains effective against HIV transmission for at least
24 hours. Accordingly the patient needs only a single daily
self-application of the composition of the present inven-
tion, to obtain the required protection. She has total and
sole control over this protection for herself, without
reliance on partners or medical practitioners.
The composition of the present invention contains
one or more emollients such as glycerine, lanolin, aloe
vera, paraffin oils, glycerol monostearate, myrj compounds,
Tween, PEG compounds, sodium lauryl sulphate, etc., and
mixtures of two or more of them, to improve the lubricity
and general oiliness of the composition. Glycerine is the
preferred emollient. It can also if desired contain various
perfumes. Any ingredients which are used must be skin
compatible, inert towards the active ingredients, and of a
nature and used in an amount which does not destabilize or
upset the general consistency of the formulation.
Sodium carbomer used as a key ingredient in the
composition of the present invention to provide the necess-
ary consistency for long lasting (minimum 24 hour) action,
is a known substance. It is the sodium salt of carbopol,
which in turn is a polymer of acrylic acid having free
carboxyl groups, which is dispersed in water to form a
slight gel. Then a suitable water soluble base such as
sodium hydroxide is added, forming a salt and affecting the
conformation of the polymer in solution and causing high
gelling effect. Various grades of carbopol are available,
having different acid values and molecular weights.
The formulations according to the present inven-
tion can be prepared using standard cosmetic or pharma-
~13~688
ceutical gel formulating procedures and equipment. There
is no particular, critical order of addition of components,
mixing temperatures or the like, provided that a homogene-
ous, reasonably stable end product is achieved.
The composition of the present invention is
useful as a spermicide and antiseptic, alone or in combina-
tion with a condom or a diaphragm. It is a topical intra-
vaginal gel which is water soluble but has the property of
remaining in the vagina for extended periods of time. It
helps protect against the transmission of various sexually
transmitted diseases such as viral (HIV or AIDS, herpes,
hepatitis B cytomegalovirus), chlamydia, trichomonas,
various bacteria including gonorrhea and G. Vaginalis and
test strain of Treponema phagedenis, a surrogate for
syphilis. It is not harmful to epithelium but will destroy
lymphocytes and macrophages which carry the AIDS virus or
HIV in persons infected with AIDS.
The composition of the present invention is
specially formulated for vaginal self-application by
females. The female adult vagina is normally about five
inches in length, and it is important that, for maximum
effectiveness, the composition be disposed all the way
along the vaginal wall, and particularly at the inner end
thereof, adjacent to the cervix. Accordingly, a preferred
embodiment of the present invention provides the composi-
tion as described above in combination with an applicator
which the patient can use to ensure proper application of
composition to the most beneficial location. The applicator
is a vaginally insertable elongated object about five
inches in length, adapted to receive and dispense the
formulation. In one preferred embodiment, the applicator
is a once usable tube containing a single dosage of formu-
lation, and has an aperture, preferably equipped with a
rupturable removable cap, provided at the distal end there-
of, i.e. the end to be disposed adjacent to the patient's
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cervix on full and proper insertion into the vagina. The
internal volume of the tubular applicator is about 8.5 ml,
which allows discharge of the appropriate dosage of compo-
sition to be administered. Normally about 5 ml of formula-
tion should be discharged. The remainder remains in, and
is discarded with, the applicator. Another form of appli-
cator is equipped with a plunger which can be operated to
empty the internal cavity of the tube through the distal
end opening. The tube is filled with the appropriate dosage
of composition, inserted fully into the vagina, and the
plunger is operated to empty it as it is withdrawn there-
from. The length of the applicator ensures that an effec-
tive amount of the composition is disposed at the cervical
end of the vagina, for maximum protection.
The specific, most preferred formulation for use
in the present invention has the following composition
(percentages by weight):
Carbopol 934P 0.40
sodium hydroxide 0.10
hydroxypropylmethyl cellulose K4M 1.50
Glycerin 2.27
Triton X-100 (octoxynol-9) 0.20
Benzalkonium chloride(MQ 2525-50~) 0.20
Water balance to 100~
The accompanying drawings diagrammatically
illustrate an applicator for use with compositions of the
present invention. The apparatus is an elongated tube of
total length about 5 inches, having an oval shape as seen
in cross section (Fig. 2) On the distal end 12 is a remov-
able or rupturable cap 14 covering an aperture 16. The
internal cavity is filled with clear gel composition
according to the invention, a quantity of about 8.0 ml. On
the proximal end 18 is an integral squeezable reservoir 20,
which is used to discharge the contents into the patient~s
2132688
vagina after full insertion of the device into the
patient~s vagina. The device is factory filled with a
single dosage, sealed at the factory, and used once and
discarded.
The invention is further described and illus-
trated in the following specific, non limiting examples.
EXAMPLE 1
o
A clear gel formulation according to specific,
most preferred embodiment of the invention as detailed
above was made. The preparation was made by simple mixing
of ingredients in a container, at room temperature. Three
normal female volunteers agreed to instill 5 ml of the
formulation intravaginally and retrieve samples of vaginal
secretions from the deep lateral wall of the vagina at
varying intervals up to eight hours after instillation. One
subject submitted samples eight hours after sexual inter-
) course (confirmed microscopically). The various samples
were assessed for anti-HIV inhibitory activity.
All specimens, even when diluted 10:1, showed
excellent activity in subsequent standard in vitro tests
against HIV-1. The similar use of a composition of the same
active ingredients but omitting the sodium carbomer, and
hence having a lotion-like consistency rather than the
semisolid gel consistency of the compositions of the
invention, yielded a secretion sample which had adequate
activity for a short period of time, but at eight hours did
not show such activity. Also, the volunteer who used it
complained that it rapidly drained from the vagina.
EXAMPLE 2
This experiment was conducted to determine the
length of time that the composition of the invention, as
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used in Example 1 above, instilled vaginally, will render
vaginal secretions sterile to HIV.
Two HIV seropositive females with previously
detectable HIV from vaginal fluids by culture and RNA PCR
were selected and studied. Both women had histories of
frequent sexual activity and intravenous drug use, T4
counts >200/cu,mm and were known to be HIV infected for
greater than 5 years. 1-2 ml of vaginal secretions were
0 aspirated with a pipette from the posterior fornix and
vaginal secretions were obtained for HIV studies. HIV RNA
PCR and HIV cultures were performed in the standard manner
(MT-2 syncytium-inhibition assay). 5.5 ml of the composi-
tion of the invention was instilled into the posterior
fornix and the women were asked to maintain normal daily
activities and to refrain from sexual intercourse. The
women were not menstruating. Prior to the installation of
the composition and after 8 and 24 hours from installation,
samples were obtained for HIV studies.
o
In both patients with previously detectable HIV
by cultures and RNA from cervical secretions, no virus was
detected for 24 hours after the application of the composi-
tion. It can thus be concluded that the composition of the
invention, when administered as described herein, is
capable of maintaining vaginal secretions sterile to HIV
for at least 24 hours.
