US2943979A

US2943979A - Concentrated foam-producing spermicides

Info

Publication number: US2943979A
Application number: US822202A
Authority: US
Inventors: Nathaniel M Elias
Original assignee: Individual
Current assignee: Individual
Priority date: 1959-06-23
Filing date: 1959-06-23
Publication date: 1960-07-05
Anticipated expiration: 1977-07-05

Description

United. States Patent CONCENTRATED FOAM-PRODUCING SPERIVHCIDES Nathaniel M. Elias, 56 Washington Mews, New York, N.Y.

N Drawing. Filed June 23, 19 59, Ser. No. 822,202

20 Claims. (Cl. 167-58) This application is a continuation-in-part of my copending application, S.N. 308,289, filed September 6, 1952, now abandoned.

The present invention relates to compositions adapted chiefly for use as topical remedies in contact with the mucous membranes in the vaginal cavity and to a method of preparing such a composition. The topical remedies of this invention comprise concentrated spermicidal compositions which are designed for use with moistened sponges or sponge-like masses such as tampons, rubber sponges, marine sponges, cellulose sponges, sponges made of cellular plastic material, etc., and which produce foam while in use.

One of the chief drawbacks to the use of spermicides has been their cost. One object of the present invention is to provide a highly concentrated spermicidal material which may be diluted with water just before use, which can be applied without the use of complex and expensive applicators, and which is not irritating to the membranes in use. The use of such highly concentrated spermicidal material cuts down paskaging, handling and shipping costs.

I have found that the use of a sponge or sponge-like mass, moistened with suflicient water to dilute the nonirritating concentrated spermicide, will give a satisfactory means for reducing the cost of application, provided (1) sufiicient spermicidal power is inherent in the concentrated spermicide, (2) suflicient foam is produced by the spermicide to distribute it thoroughly throughout the vaginal canal, and (3) the composition mixes quickly with seminal fluid. The foam producing property is highly important as a means of distribution of the spermicidal liquid. The moist sponge acts as a vehicle for distribution of the spermicidal liquid and as a reservoir for foam production.

I have also found that concentrated solutions of high spermicidal and foam-producing power may be obtained which are not irritating. This may be done with certain water-soluble non-ionic and foam-forming agents whose pH can be regulated to any point required and solutions of which are compatible with various salts and acids. These products which I have found to possess high spermicidal power are sufliciently foam-forming only in the absence of insoluble ingredients and belong to the class represented by the generic formula R OCHzOHz O 011101191011 irritation in use with a moistened sponge.

average value between 8 and 12. In the preferred specific embodiment of my invention x is approximately 9.75, R is either the triisopropyl group or the tetraethyl group and is in the para position and R is hydrogen;

Generally R may have from 1 to 23 carbon atoms and R may have fiom O to 23 carbon atoms except that the sum of the carbon atoms in R and R should not be less than 4 or more than 23.

An important advantage of using these materials is the fact that solutions containing them are neutral and may be adjusted to any pH value, and that they do not react with weak acids or alkalis or with buifer salts or neutral salts.

The quantity of active spermicide described above in Formula 1 which may be employed in the present composition will vary considerably. In a preferred practice of this invention it will constitute from 15 to by weight of the total composition.

I have found that certain neutral salts such as sodium or potassium chloride or sulfate or other similar salts are valuable additions to these compositions in that they increase enormously the speed of miscibility of the nonionic foam-forming spermicidal materials with seminal fluid so that quick spermicidal action is assured. These neutral salts desirably constitute 5% to about 20% by weight of the spermicidal composition.

By using the materials of this invention, I have found it easily possible to make solutions, 30 grams of which are ample for 60 or more applications, free of resulting Even higher concentrations are practicable.

The method of application is simple also in that a glass, plastic, wooden or similar rod may be moistened with the solution and then rubbed on the moistened sponge. This may be repeated three or four times, the material being applied on all sides. For example, /2 cc. may be so transferred very quickly and easily. As an example of the sponge mass which may be used, a sheet of rubber sponge about thick by 2" square would be suitable. It will act as a reservoir for 3-5 cc. of water. After the transfer of the spermicidal and foam-forming concentrate to it, it is slightly compressed and released several times to mix the solution into the water in the sponge. It thus distributes the concentrated liquid throughout the water stored in the sponge before insertion. It is of course also possible to apply the concentrated liquid to the sponge in other Ways, such as by the use of an eye dropper, dropping tube, scoop or brush. It is generally convenient to have the means of applying the liquid to the sponge attached to the closure of the container and extending into said container.

Tests have shown that the moisture in the sponge, as used, may range between /2 cc. and 3 cc. so that when a solution containing 15% of the active spermicidal agent is applied to the sponge in an amount of A2 cc., the resulting concentration which is used topically may range from 7 /2% to 2.14%. If a 20% solution is applied to the wet sponge under these conditions in the amount of /2 cc., the resulting solution which is used topically may range from 10% to 2.86%.

I am aware that some of the polyglycol monoethers of alkyl phenols have been'used in spermicidal jellies and suppositories. However, they have always been used in the presence of insoluble materials such as ricinoleic acid, glyceryl moonlaurate, vegetable and other gums, etc., or in the presence of strong spermicidal materials such as phenyl mercuric acetate, etc., to enhance the eifectiveness of these other spermicides. There has been no disclosure that they are spermicidal in themselves not that they can be used in high concentrations without causing irritation. In addition, the presence of insoluble materials inhibits foam formation so that the: teaching of these previous disclosures would be insufiicient for the development of the present invention since foam formation is essential to its proper functioning. I have now found it possible to obtain with these materials both high sperrni: cidal power and high foam-forming power simultaneously Without the use of heavy metal or other spermicides.

In addition, by' using aneutral salt such as sodium chloride in conjunction with these materials,- I have found a great increasein the speed of, mixing of the spermicide withv semenfthus resulting in 'a substantial increase in efiectiveness. V 7

' Glycerine; propylene glycol or ,other polyhydroxy compoundsor urea may be added to any of the formulae in theexamplesgiven below to prevent freezing in cold Weather. 7

Since no gums are present in any of the formulae nor any substances which may cause mold formation, no mold inhibiting material is necessary for this purpose. However, such substances as methyl, ethyl, propyl or butyl parahydroxy benzoate, oxyquinoline sulfate, phenols, alkyl phenols, chlorinated phenols, chlorinated thymols, the alkali alkyl sulfate, etc., may be used for their bacten'iostatic and fungistatic effect;

Water soluble acids with or without buffer salts may be used to regulate the pH value. The pH value of the compositions of'the present'invention may range'bc tween 1 and 8.5although'a pH of about 4.5 (the nor= mal'pH- ofthe vaginal membranes) is preferred. The limitations on the pH are placedin this range simply because in this range the chances of irritation are less than at higher or lower pH values and a pH in this range is less favorable for invasion by undesirable organisms.

' The acids which may be used include among others lactic, boric, acetic, tartaric, etc;, and the buffer salts include sodium or'potassium salts 'of these acids as well as of'phosphori'c acid and others. j p

The following are typical examples of concentrated foam-producing spermicidal compositions suitable for effective use with a wet sponge mass or tampon.

Example 1 Parts by wgt.

p-Triisopro'pyl phenyl monoether of nona ethylene Water sufficient to make a total of 100.00 parts by weight.

Example 2 A concentrated foam-producing spermicidal composition having the same formula as Example 1 but in which the p-triisopropyl phenyl monoether of nona ethylene glycol is replaced with a mixture consisting of the p-triisopropyl phenyl monoether of nona ethylene glycol and the p-triisopropyl phenyl monoether of dodecaethylene glycol.

Example 3 A concentrated foam-producing spermicidal composition having the same formula as Example 1 but in which the p-triisopropyl phenyl monoether of nona ethylene glycol is replaced by p-tetraethyl phenyl monoether of dodecaethylene glycol. r r i V 1 Example 4 A concentrated foam-producing spermicidal composition having the same formula as Example 1 but in which part of the p-triisopropyl phenyl monoether of nona ethylene glycol is replaced by p-tetraethyl phenyl monoether of nona ethylene glycol. 7

Example p A concentrated foam-producing spermicidal composition having the same formula as Example l'except that the proportion of sodium chloride is increased from 5% to 10%.

Example 6 A concentrated foam-producing spermicidal composition having the same formula as Example 1 in which the lactic acid is replaced by 1.5 parts of boric acid.

Example 7 A concentrated foam-producing spermicidal composition having the same formula as Example 1 in which the lactic acid is replaced by 1.5 parts of boric acid and the sodium lactate is replaced by 1.5 parts of sodium borate.

When /2 cc. of any of the compositions described in the above examples is applied to a sponge containing 5 cc. of water, the resulting solution comes well within the spermicidal requirements recommended by the Council of Pharmacy of the A.M.A., using the Brown & Gamble technique.

The compositions included in this invention may be shipped constituted as described in the aforesaid examples or may be shipped in even more concentrated form to remote countries or localities and there they may be diluted and packed in containers of local origin. The following are examples of such higher concentrates.

SHIPPING CONCENTRATES Example 8 p-Triisopropyl phenyl monoether of nona ethylene glycol -a- Lactic acid 3.0 Sodium lactate 3.0 Sodium chlorid 10.0

Water sufiicient to make a total of 100.0.

Example 8 is twice the concentration of Example 1. On arriving at its destination, it may be diluted with an equal quantity of water, giving the formula of Example 1.

Water sufficient to make 100.0.

Example 9 requires the addition of 300 parts of a sodium chloride solution containing 15 parts of salt to ob tain a composition identical with that in Example 1 Example 10 p-Triisopropyl phenyl monoether of nona ethylene glycol a V Boric acid 5 Sodium chloride 20 On diluting this with 400 parts of water there would be obtained a product suitable for use containing: p-Triisopropyl phenyl monoether of nona ethylene y l w 7 7 15 Boric acid Sodium chloride 4 It is obvious that by using such concentrates for shipping purposes freight, container and other shipping costs are greatly reduced.

Example 11 p-Triisopropyl phenyl monoether of nona ethylene I V glycol 20 Boric acid 1 7 3 Sodium chloride 1'6 Water suific-ient to make 100.

v Example 12 p-Triisopropyl phenyl monoether of nona ethylene glycol 20 Boric acid 3 Propyl p-hydroxybenzoate .2 Sodium chloride Water sufficient to make 100.

The spermicidal composition of the present invention may be prepared for application to a sponge-like mass by mixing a concentrated water solution of a non-ionic, foam-producing, surface active agent of the class represented by the formula Parts by wgt.

p-Triisopropyl phenyl monoether of nona ethylene glycol Lactic acid 1.5 Sodium lactate 1.5 Sodium chloride 5 Water suflicient to make a total of 100 parts by weight.

The Brown & Gamble technique consists of mixing one part of the spermicidal material with four parts of physiological saline solution. The resulting mixture is then mixed on a slide with an equal volume of human semen and the time for complete immobilization is observed.

One-half cc. of the above composition was mixed with 5 cc. of water in a sponge, after which 1 part of the resulting solution was taken from the sponge and diluted with 5 parts of physiological saline solution. One part of this final solution was then mixed with an equal volume of human semen on a slide, and the time for complete immobilization was observed.

Complete immobilization of the sperm resulted in less than five minutes.

The effectiveness of said solution comes well within the spermicidal requirements recommended by the Council of Pharmacy of the American Medical Association using the Brown & Gamble technique. This requirement is that immobilization occur in thirty minutes or less.

The clinical safety of the compositions of the present invention were tested by the Margaret Sanger Research Bureau. The spermicide tested had the following composition:

7 Parts by wgt. p-Triisopropyl phenyl monoether of nona ethylene glycol Boric acid 3 Propyl p-hydroxybenzoate .2 Sodium chloride 10 Water sufiicient to make 100 parts by weight.

examination was performed and all findings were recorded. Particular attention was paid to the condition of the vulva, vaginal and cervical mucosa. The women were instructed to insert the foam filled sponge nightly for a period of 21 days. A string was attached to the sponge for easy removal. The patient was instructed to make a careful note of any evidence of irritation. Vaginal examinations were made twice weekly as well as after the test period was completed and all objective findings were recorded.

There was no complaint of irritation in 11 patients. One complained of slight itching.

There were no objective signs of irritation in any of the 12 subjects.

To further test the clinical safety and efiectiveness of the present composition the following clinical experiments were carried out at the St. Elizabeth Health Department in Black River, Jamaica, B.W.I. The spermicidal composition used in these experiments are identified as Duratoam Liquid and consists of a water solution containing In said clinical experiment Durafoam Liquid was distributed to patients with instructions as to its use. It was dispensed with a small sponge and the patients were instructed that said sponge is to be moistened on both sides with /2 cc. of said Durafoam Liquid before insertion and use. The Durafoam Liquid was distributed to patients in a small dropper bottle to make measurement easy and the patients were instructed to bring the bottles back to be refilled. The patients were instructed to return when they required additional material. The public health nurses of St. Elizabeth Health Department were used in this experiment for distribution of the Durafoam Liquid and to follow up patients who were using it.

Set forth below in Table I is a report of the above described clinical experiment covering a period of 18 months.

TABLE I Total patients given Durafoam Liquid with sponge 640 Total patients discontinued use of Durafoam Liquid Multiplying the figure 571 by 9 and dividing by 12 gives 428 woman years use with 18 pregnancies. This is 4.2 pregnancies per 100 woman years. The normal rate in this population is between 70 and per woman years. The Durafoanr Liquid therefore reduces the pregnancy rate very substantially. Of the 69 patients who discontinued the use of the method 18 became pregnant. Of these 18, 12 admitted irregular use and 4 stated that their husbands objected to the presence of the sponge. Fifty-one discontinued either because they were planning a pregnancy or were indifferent and did not want to be bothered with using the method.

Theresults of these tests indicate that the present spermicidal composition with sponge is a very effective method for reducing the pregnancy rate and is well adapted for use in rural areas where education is at a low level. It is also quite evident that the alkyl phenoxy polyethoxyethanols are highly and eifectively spermicidal in use and especially so in the presence of a salt.

While the invention has been described with particular reference to specific embodiments, it is to be understoodthat it is not limited thereto, but is to be construed broadly 7 and restricted solely by the scope of the appended claims.

What is claimed isi: r 1'. spermicidalcomposition consistingessentially ofa buttered pharmaceutical vehicle and asi'chief spermicidal ingredient an alkylplienoxypolyethoxyethanol of the formula QUIET- 2 lix-C 2) x011.

hydrogen, and R is para to the group OCH CH (OCH CH OH and from &to, 12carboncatoms in the chain, andxhas ahfaveragevalue. oftromabouLG. to. about. 12. i A

'3. A composition according tosclaim 2. wherein said, compositionasiappliedtopically.contains from about 2%. to 10%. of said .alkylphenoxypolyethoxyethanol.

I41 A composition; according to claim 1 wherein. the alkylphenoitypolyethoxy thanol is, a mixture of, p-alkylphenoiiypolyethokyethanols wherein'R is hydrogen,

andR has from 8to 12.-carbon, atomsin the chain and x r average'value oi from'about 6, to about 12. 5. composition' according; tojclaim 1 wherein said chief spermicidal'iii'gredient is -p-triisopropyl phenylrnonor ether" ofrioriafethyleneglycol. 5 i

6Q A'spermic'idab'coniposition according to claim 1 wherein the vehicleicontains' T si rmiidal .compos tio according to l i l wherein said vehicle'contain's' bofic acid.

8. A spermicidal compositionconsisting essentially, of

a, buffered pharmaceutical vehicle and containing, as; its

chief spermicidal active ihgredie'nt a 'com'pouiid the,

general formula vh ia RI e esents, a lk l group hav from 1 to 23 carbon atoms in th e chain and R represents a member q e irqml q as u s st a o l y up v from [to '23 carbon atoms and hydrogen, and x has an average value of from about 5 to about 12, and wherein saideomposition'havihg a pH in the range about 1 to about 85 inclusive.

a 9, A composition according to claim 8 wherein the spemiicidally. active ingredient is present in the rangeof about 15. to 75% by weightof thespermicidal compositlon. a

1 0.. A composition accordingto claim' 8 wherein the spermlcidally active ingredient is present in an amount of. 15% by weight ofthe spermicidalcomposition.

11. A spermicidal composition according to claim 8 wheremithespermicidally active ingredient is present in an amount of'30 bjweight of the spermicidal composition.

,12. Aispehmicidal composition according to claim 8 wherem spermicidallyfactive ingredient is present in 8 an amount of 60% by weight of the spermicidal composition.

13. A spermicidal composition accordingv to whereinthe' spermicidallyactive ingredient is presentzin the" amount of by wight'of the 'spermicidalcomposi;

tionJ i "14. A spermicidal composition consisting essentially of a hydrous pharmaceutical vehicle containing as it's;

chief spermicidally active ingredient a compound 'of the a general formula wherein R represents an alkyl group having from 1 to 23 carbon atoms in, the chain and R represents a member selected from the class consisting of alkyl groups having from 1 ito 23 carbon atoms and hydrogen, and x has an average valueof from about itoabout 12, and wherein the. of. thecarbon atoms :i n.. R andR; is not.

4 or greater 23, saidspefrmicidally active ing riedient;

asere sm- 5} 3 s d atema t a sent i ng sti n ha ng. a 12H; n e an e ir n about 1 to about inclusive.

15. A spermicidal composition consisting essentially oi a tte e rmaswfi a i e-an ta n te- 1 plied topically, from 2% to. 1 0% of a compou dfof gen; eral formula i m wherein R represents an alkyl group having from 13 ,223

carbon atomsin the chain and li frepresents agmenrber,

OCHr-CH2(O orig-501191011;

wherein R. represents, an, alkyl: group. haying from 1: 19. 2.3: carbon: atoms inrthe chain andR represents a, member; selected, from the class consisting of alkyl groups, haying, from 1 to.23 carbon atoms and hydrogen, and x hasgan j average, value of firomabout 5. to about, 12, and;wherein the sum of the carbonatomsinR; and; R is .n o,t less than 4 or greater than 23, said; concentrate, J i u i nthe water in the moist sponge, having a pH in therange from about; 1, to about 8.5 inclusive.

17; A. spermicidal method: which comp isi app y n toa wet, sponge-like. mass avliquid,snermi iial QQI QQ Y trate containing. a neutralsalt and f -he chief. nemiq h ally active ingredientv av compound; of; the generalfo1;-,, mula, 7

from 1 to 23 carbon atoms andghydrogen, and x hast average value of from about 5 to 12, and wherein the sum of the carbon atoms in R and R is not less than 4 or greater than 23, and applying the resulting spermicidally treated sponge-like mass into the vaginal cavity in contact with the mucous membranes to serve as a topical remedy.

18. A spermicidal method which comprises introducing into the vaginal cavity a spermicidal composition consisting essentially of a pharmaceutical carrier and as chief spermicidal ingredient an alkylphenoxypolyethoxyethanol of the formula O CHr-CH (O GH -CHI) :OH

wherein R represents an alkyl group having from 1 to 23 carbon atoms in the chain and R represents a member selected from the class consisting of alkyl groups having from 1 to 23 carbon atoms in the chain and hydrogen, and x has an average value of from about 5 to about 12, and wherein the sum of the carbon atoms in R and R is not less than 4 or greater than 23.

19. A method according to claim 18 wherein R ishydrogen and R is para to the group and has from 8 to 12 carbon atoms in the chain, and x has an average value of from about 6 to about 12.

29. A method according to claim 19 wherein said composition as applied topically contains from about 2% to 10% of said alkylphenoxypolyethoxyethanol.

References Cited in the file of this patent UNITED STATES PATENTS 1,970,578 Schocller et a1 Aug. 21, 1934 2,213,477 Steindorff et al Sept. 3, 1940 2,436,184 Stillman et a1 Feb. 17, 1948 2,467,884 Elias Apr. 19, 1949 2,541,103 Sander Feb. 13, 1951 2,556,567 Wright June12, 1951 2,889,250 Mende et a1. June 2, 1959 OTHER REFERENCES De Vilbiss: J. Contraception, January 1938, pp. 7-9 and 19.

N.N.R.: 1951, Phila., Pa, pp. xxxi-mii.

Claims

1. A SPERMICIDAL COMPOSITION CONSISTING ESSENTIALLY OF A BUFFERED PHARMACEUTICAL VEHICLE AND AS CHIEF SPERMICIDAL INGREDIENT AN ALKYLPHENOXYPOLYETHOXYETHANOL OF THE FORMULA