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Description  |
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The present invention relates to the field of contraception and is
specifically concerned with preventing fertility in mammals, particularly
the human female, by means of the use of locally applied chitosan, to-wit,
in the uterine cavity, in a form effective to prevent the fertilization of
the ovum by the spermatozoa, particularly human male sperm under
conditions and in a form such as to prevent conception.
It has long been known to prevent fertility in human and other animal
females by locally acting agents since their use, if at least reasonably
effective, avoids the problems and complications which not infrequently
result from such procedures as utilize mechanical devices such as
intrauterine shields which are placed into the uterus, or systemically
acting compositions such as the orally administered steroid hormones or
birth control pills. Such mechanical devices have numbers of disadvantages
and the same is true of the use of steroids, which disadvantages are well
known to the art.
Many locally applied contraceptive agents have long been known or suggested
by the art, including various metal compounds, and spermacide-containing
compositions which are inserted in the vagina shortly prior to intercourse
and which generate a spermacide-containing foam. The deficiencies of such
metal compounds and spermacide-containing compositions are, likewise, well
known to the art.
In accordance with the present invention, chitosan is utilized as a
spermatastat which prevents the spermatazoa from penetrating and
fertilizing the ovum and is applied locally by insertion in the uterine
cavity in the manner described below.
Chitosan is deacetylated chitin. Chitin, the source material for citosan,
is a cellulose-like polymer present in fungal cell walls and exoskeletons
of arthropods such as insects, crabs, shrimps and lobsters, and it is
produced in large quantities particularly from waste shells of crabs and
shrimps. Depending upon its molecular weight, it is soluble or insoluble
in water. Likewise, based upon its molecular weight, its solubility varies
in different commercial solvents.
Chitosan, which, as stated above, is prepared by deacetylating chitin, is
soluble in dilute formic, acetic, pyruvic, lactic and malic acids, and
inorganic acids, were the solute is water, water-methanol, water-ethanol,
water-acetone and similar diluents. In various acidic solvents, chitosan
forms viscous non-Newtonian solutions. The solution viscosities of
chitosan depend upon its molecular weight, the extent of deacetylation of
the chitin, concentration and types of solvents, and temperature. As
solution temperature increases, viscosity decreases. Viscosity retention
is compatible with that of carboxymethyl cellulose. The foregoing facts
are well known to the art.
Chitosan has heretofore been used and/or suggested for use for a wide
variety of purposes, including, by way of illustration, for flocculating
bacteria, yeasts and microfungi from suspensions containing the same; for
flocculation of industrial wastes such as proteins in liquid wastes from
packing houses, poultry, fish and vegetable processing plants, whey,
leather tanning wastes, Kraft paper mill wastes and suspended solids from
mine tailings; for preparing membranes which have ion exchange properties
and with various permeability properties in regard to moisture and gases
such as oxygen, nitrogen and carbon dioxide; for chelation and for column
chromatography metal, enzyme and virus separation procedures; as viscosity
builders for various foods, cosmetics, drugs, etc.; for broad spectrum
antifungal uses such as preventing the growth of pathogenic fungi which
normally infect peas and other plant products; for inhibiting the
fermentation of yeasts in various food products; and for application to
seeds prior to planting to prevent fungal diseases. It is also known that
chitosan solutions are similar in certain of their characteristics and
properties to cellulose ethers, functioning as thickeners, stabilizers and
suspending agents. Based upon tests reported in the literature, chitosan
is non-toxic and, indeed, is found in and has been used and suggested, as
noted above, for use in various food products.
While chitosan is found in the cell walls of some fungi, it is prepared
commercially by deacetylation of chitin in a variety of known ways such
as, for instance, by certain plant enzymes. The extent of deacetylation of
chitin to produce chitosan is variable. For use of chitosan for the
contraceptive purposes of the present invention, it is unnecessary that
the chitin be deacetylated sufficiently to allow dissolving it in the
recommended solvent. A commercially available partially deacetylated
chitin is partially deacetylated (about 16%) glucoseamine polymer,
.beta.-(1-4)2-acetamido-2-deoxy-.delta. glucose, which is acetylated
chitin containing about 7.5% nitrogen, and being about 80% deacetylated.
Chitosans having higher percentages of deacetylation can be used, as well
as lower percentages of deacetylation, but, generally speaking, it is
preferred that the percentage of deacetylation do not fall lower than
about 65%. The unreacted chitin is not harmful but it is fundamentally
inert in its contraceptive properties and, therefore, relatively high
percentages of chitin in the chitosan are undesired.
In order for the chitosan to act most effectively to prevent the sperm from
penetrating the ovum, the chitosan molecules must be motile. For this
reason, for optimum results, the chitosan molecules should be in the form
of a solution or the like as distinguished from being used in powder form.
As indicated above, where the chitosan is in a form in which it is
insoluble in water, it is conveniently used by dissolving it in dilute
solutions of non-toxic acidic materials and acids which are also
non-irritating to the delicate tissue of the walls of the intrauterine
cavity. Dilute solvent solutions of chitosan in such acids as, for
example, formic, acetic, propionic, butyric, malic, fumaric, succinic,
pyruvic, lactic, acetic, D-Glucuronic, D-Galacturonic and D-Mannuronic
acids afford functionally effective compositions for use in accordance
with the present acid. While dilute inorganic acid solutions of chitosan
can also be used, from a functional standpoint, their use is distinctly
less preferable because of the generally adverse effect of the inorganic
acids on the tender tissues of the walls of the intrauterine cavity.
Especially satisfactory as a solvent for the chitosan is ascorbic acid
since it tends to provide for better penetration of the chitosan and to be
tolerated more satisfactorily by the body than at least most of the other
acids.
The amount of the acidic material or acid required to dissolve the chitosan
is variable, depending upon the particular chitosan utilized, within wide
limits, as, for instance, from 5 ppm to 10%. Once the chitosan is
dissolved, it can be diluted to a very low level, depending on the manner
in which the chitosan composition is utilized. If it is to be employed in
the form of a gel, the chitosan content of the contraceptive composition
can be in the range of about 1% to about 5%, by weight, in aqueous
solutions of, for instance, 1% to 3% of acetic acid or ascorbic acid. If
the chitosan serves to provide all of the gelling action, the higher
levels of chitosan disclosed above are particularly desirable. If a
separate gelling agent is used, then levels of chitosan lower than 1% can
be employed. Over and above such use where it is placed into the
intrauterine cavity for retention over relatively prolonged periods of
time, the chitosan compositions can also be used as douches in which case,
by way of illustration, suitable formulations can comprise from about
0.25% to about 1.5%, by weight, in aqueous solutions of, for instance,
0.25% to 1.5% of acetic acid or ascorbic acid.
The concentration of the chitosan in the solution or the gel for preventing
conception is variable and, in general, will range from a level of about
5% down to about 10 ppm. In this connection, it is important to taken into
account that the chitosan tends to be tied up by the proteins which are
present in the vagina and uterus as a result of the seepage of such
proteins into the solutions or gels in the intrauterine cavity. There is,
therefore, required to be sufficient chitosan available in the vagina and
uterus to overwhelm the mucal proteins which are present and still leave
sufficient chitosan molecules to inactivate or tie up the enzymes present
which would otherwise allow the sperm to penetrate the ovum.
Another factor which is to be taken into account is the molecular weights
of the chitosans which are utilized. The molecular weights, generally
speaking, of the chitosans as produced or which are normally produced will
tend to fall within the range of about 30,000 to about 300,000. High
molecular weight chitosans form solutions with higher viscosities than
chitosans of lower molecular weight. With high molecular weight chitosans,
say about 300,000, a gel is produced in dilute aqueous solutions of acidic
materials or acids with as little as 1%, by weight, of such chitosans. On
the other hand, with chitosans having molecular weights as low as about
30,000, in dilute aqueous acidic or acid solutions, about 5% to about 10%
solutions, by weight, of such chitosans produce solutions having a
relatively low viscosity.
It will, of course, be recognized that the chitosan, in the form of
solutions or gels, can be incorporated with other materials to produce
compositions having variant viscosities, as well as with supplemental
materials such as perfumes and colorants, as well as active ingredients.
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