A method for treating sexual dysfunction that is caused by anti-depressant medication in a patient in need of such treatment, comprising administering a therapeutically effective amount of apomorphine, or a pharmaceutically acceptable salt thereof to said patient, is disclosed. The method may be utilized for patients taking anti-depressants such as tricyclic anti-depressants, monamine oxidase inhibitors or serotonin selective reuptake inhibitors.

The present invention is directed to a method for treating sexual dysfunction in a patient taking anti-depressant medication in need of such treatment comprising administering a therapeutically effective amount of apomorphine or a pharmaceutically acceptable salt thereof to said patient. The method may be utilized for patients taking anti-depressants such as tricyclic anti-depressants, monamine oxidase inhibitors or serotonin selective reuptake inhibitors.
Depression is a chronic illness that affects people of all ages. Tricyclic antidepressants, monamine oxidase inhibitors, and selective serotonin reuptake inhibitors are classes of drugs which are prescribed for the treatment of depression. Tricyclic anti-depressants include imipramine hydrochloride, imipramine pamoate, amitriptyline hydrochloride, desipramine hydrochloride and protriptyline hydrochloride. Monamine oxidase inhibitors include isocarboxazid, phenelzine sulfate and tranylcypromine sulfate. Of the various classes of anti-depressants currently available, the selective serotonin reuptake inhibitors (SSRI""s) are among the most successful.
SSRI""s include fluoxetine, fluvoxamine, citalopram, cericlamine, femoxetine, ifoxetine, cyanodothiepin, seritraline, paroxetine and litoxetine. Anti-depressants have many undesirable side effects, such as disturbance of sexual function. Since sexual dysfunction is common in depression as part of the underlying disease, the use of a drug to treat depression which may further cause sexual dysfunction is particularly objectionable.
A variety of strategies have been reported in the management of SSRI-induced sexual dysfunction, including waiting for tolerance to develop, dosage reduction, drug holidays, substitution of another anti-depressant drug, and various augmentation strategies (addition of another drug) with 5-HT2, 5-HT3 and xcex12 adrenergic receptor antagonists, 5-HT1A and dopamine receptor agonists and phosphodiesterase enzyme inhibitors, as disclosed by Rosen et al. in J. Clin. Psychopharmacol. Vol. 19, No 1, pp.67-84.
Augmentation strategies may include co-treatment with cyproheptadine, bethanecol, yohimbine, amantadine, alprazolam, chlordiazepoxide, clonazepam, diazepam or lorazepam according to Forman et al., xe2x80x9cDrug-induced infertility and Sexual Dysfunctionxe2x80x9d in Textbook of Erectile Dysfunction, Oxford: Isis Medical Media Ltd, 1999, pp. 40-43; co-treatment with Ginkgo Biloba as disclosed in U.S. Pat. No. 5,897,864; or co-treatment with sidenafil, according to Fava et al., xe2x80x9cAn Open Trial of Oral Sildenafil in Antidepressant-Induced Sexual Dysfunctionxe2x80x9d, Psychother. Psychosom., 1998, 328-331.
Nevertheless, there is still a need for effective medications which can be used to treat sexual dysfunction in patients taking anti-depressants.
It is therefore an object of the present invention to provide a method for the treatment of sexual dysfunction in patients taking anti-depressants, to treat the condition potentially caused by the depression and exacerbated by the anti-depressant.
The present invention is directed to a method of treating sexual dysfunction in a patient taking anti-depressant medication in need of such treatment comprising administering a therapeutically effective amount of apomorphine or a pharmaceutically acceptable salt thereof to said patient. The anti-depressant medication may be a tricyclic anti-depressant, a monamine oxidase inhibitor or a serotonin-selective reuptake inhibitor. Preferably, the therapeutically effective amount of apomorphine is an amount wherein a concentration of apomorphine is attained within said patient""s plasma of up to 10 nanograms per milliliter.
If the patient is male, the therapeutically effective amount may be an amount sufficient to induce an erection adequate for vaginal penetration. Alternatively, if the patient is female the therapeutically effective amount may be an amount sufficient to induce clitoral erectogenesis and vaginal engorgement. Preferably, the therapeutically effective amount is insufficient to produce emesis. However, if larger (potentially emesis-inducing) doses are required, the apomorphine may be co-administered with an emesis-inhibiting amount of an anti-emetic agent.
The anti-emetic agent may be nicotine, lobeline sulfate, metoclopramide, chlorpromazine, prochlorperazine, pipamazine, thiethylperazine, oxypendyl hydrochloride, domperidone, ondansetron, buclizine hydrochloride, cyclizine hydrochloride, dimenhydrinate, scopolamine, metopimazine, trimethobenzamide, benzauinamine hydrochloride or diphenidol hydrochloride.
In the method, apomorphine may administered intranasally, orally ingested, sublingually or administered by inhalation to the lungs. Moreover, the apomorphine may be administered as a pharmaceutically acceptable salt, preferably the hydrochloride salt.
In males, the form of sexual dysfunction is erectile dysfunction. A normal erection occurs as a result of a coordinated vascular event in the penis. This is usually triggered neurally and consists of vasodilation and smooth muscle relaxation in the penis and its supplying arterial vessels. Arterial inflow causes enlargement of the substance of the corpora cavemosa. Venous outflow is trapped by this enlargement, permitting sustained high blood pressures in the penis sufficient to cause rigidity. Muscles in the perineum also assist in creating and maintaining penile rigidity. Erection may be induced centrally in the nervous system by sexual thoughts or fantasy, and is usually reinforced locally by reflex mechanisms. Erectile mechanics are substantially similar in the female for the clitoris.
Impotence or male erectile dysfunction is defined as the inability to achieve and sustain an erection sufficient for intercourse. Impotence in any given case can result from psychological disturbances (psychogenic), from physiological abnormalities in general (organic), from neurological disturbances (neurogenic), hormonal deficiencies (endocrine) or from a combination of the foregoing. Impotence may be hormonal, congenital, vascular or partial ability, among others.
These descriptions are not exact, however. There is currently no standardized method of diagnosis or treatment. As used herein, psychogenic impotence is defined as functional impotence with no apparent overwhelming organic basis. It may be characterized by an inability to have an erection in response to some stimuli (e.g., masturbation, spontaneous nocturnal, spontaneous early morning, video erotica, etc.) but not others (e.g., partner or spousal attention).
Females also can have sexual dysfunction that increases with age and is associated with the presence of vascular risk factors and onset of menopause. Some of the vascular and muscular mechanisms that contribute to penile erection in the male are believed to be similar vasculogenic factors in female genital response. It is known that in women, sexual arousal is accompanied by arterial inflow which engorges the vagina and increases vaginal lubrication and that the muscles in the perineum assist in achieving clitoral erection.
In the female, sexual dysfunction can arise from organic and psychogenic causes or from a combination of the foregoing. Female sexual dysfunction includes a failure to attain or maintain vaginal lubrication-swelling responses of sexual excitement until completion of the sexual activity. Organic female sexual dysfunction is known to be related in part to vasculogenic impairment resulting in inadequate blood flow, vaginal engorgement insufficiency and clitoral erection insufficiency.
Apomorphine ((R)-5,6,6a,7-tetrahydro-6-methyl-4H-dibenzo-[de,g]quinoline-10,11-diol) can be represented by the formula
and exists in a free base form or as an acid addition salt. For the purposes of the present invention, apomorphine hydrochloride is preferred, however other pharmacologically acceptable salts thereof can be utilized as well.
Apomorphine can be used in the form of pharmaceutically acceptable salts derived from inorganic or organic acids. The phrase xe2x80x9cpharmaceutically acceptable saltxe2x80x9d means those salts which are, within the scope of sound medical judgement, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well-known in the art. For example, S. M. Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66: 1 et seq. The salts can be prepared in situ during the final isolation and purification of the compounds of the invention or separately by reacting a free base function with a suitable organic acid. Representative acid addition salts include, but are not limited to acetate, adipate, alginate, citrate, aspartate, benzoate, benzene sulfonate, bisulfate, butyrate, camphorate, camphor sulfonate, digluconate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethansulfonate (isothionate), lactate, maleate, methane sulfonate, nicotinate, 2-naphthalene sulfonate, oxalate, palmitoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, phosphate, glutamate, bicarbonate, p-toluene sulfonate and undecanoate salts. Also, the basic nitrogen-containing groups can be quaternized with such agents as lower alkyl halides such as methyl, ethyl, propyl, and butyl chlorides, bromides and iodides; dialkyl sulfates like dimethyl, diethyl, dibutyl and diamyl sulfates; long chain halides such as decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides; arylalkyl halides like benzyl and phenethyl bromides and others. Water or oil-soluble or dispersible products are thereby obtained. Examples of acids which can be employed to form pharmaceutically acceptable acid addition salts include such inorganic acids as hydrochloric acid, hydrobromic acid, sulphuric acid and phosphoric acid and such organic acids as oxalic acid, maleic acid, succinic acid and citric acid.
Apomorphine has been disclosed as useful in intranasal formulations for the treatment of Parkinson""s disease in U.S. Pat. No. 5,756,483.
Apomorphine transdermal administration has been disclosed in U.S. Pat. No. 5,939,094; and apomorphine in capsule form has been disclosed in U.S. Pat. No. 5,866,164.
Apomorphine is a dopamine receptor agonist that has a recognized use as an emetic when administered subcutaneously in about a 5 milligram dose. For the purposes of the present invention, apomorphine is administered in an amount sufficient to excite cells in the mid-brain region of the patient but with minimal side effects. This cell excitation is believed to be part of a cascade of stimulation that is likely to include neurotransmission with serotonin, dopamine and oxytocin.
The dopamine receptors in the mid-brain region of a patient can be stimulated to a degree sufficient to cause an erectile response without inducing nausea by the administration, preferably sublingually, of apomorphine so as to maintain a plasma concentration of apomorphine of no more than about 5.5 nanograms per milliliter (5.5 ng/ml). The sublingual administration usually takes place over a period of time in the range of about 2 to about 10 minutes, or longer. The amount of apomorphine administered sublingually over this time period preferably is in the range of about 25 micrograms per kilogram (xcexcg/kg) of body weight to about 60 xcexcg/kg of body weight.
In sensitive patients experiencing nausea, the onset of nausea can be obviated or delayed by delivering apomorphine at a controlled dissolution rate so as to provide circulating serum levels and midbrain tissue levels of apomorphine less than 5.5 nanograms/mL. When apomorphine is administered at or near the higher amounts of the aformentioned dosage range, the likelihood of the onset of nausea can be reduced by concurrent administration of a ganglionic agent (inhibitor of ganglionic response and anti-emetic agent) such as nicotine or lobeline sulfate. For this purpose, the weight ratio of apomorphine to ganglionic agent is in the range of about 10 to 1.
Other anti-emetic agents that can be used in conjunction with apomorphine are anti-dopaminergic agents such as metoclopramide, and the phenothiazines, e.g., chlorpromazine, prochlorperazine, pipamazine, thiethylperazine and oxypendyl hydrochloride among others. Also suitable are the serotonin (5-hydroxytryptamine or 5-HT) antagonists such as domperidone, ondansetron (commercially available as the hydrochloride salt under the designation ZOFRAN) among others, the histamine antagonists such as buclizine hydrochloride, cyclizine hydrochloride, dimenhydrinate (DRAMAMINE) among others, the parasympathetic depressants such as scopolamine, as well as other anti-emetics such as metopimazine, trimethobenzamide, benzauinamine hydrochloride, and diphenidol hydrochloride among others.
The term xe2x80x9cco-administeredxe2x80x9d used herein indicates treatment with two or more pharmacological agents together in a single unit dosage form or alternatively, in two or more separate unit dosage forms, one immediately following the other.
The apomorphine according to the invention can be administered as a nasal spray, nasal drop, suspension, gel, ointment, cream or powder. The administration of the nasal composition may also take place using a nasal tampon or nasal sponge.
Powders can be administered using a nasal insufflator. Powders can also be used in such a manner that they are placed in a capsule. The capsule is set in an inhalation or insufflation device. A needle is penetrated through the capsule to make pores at the top and the bottom of the capsule, and air is sent to blow out the powder particles. Powder formulations can also be administered in a jet-spray of an inert gas or suspended in liquid organic fluids.
Sublingual apomorphine dosage forms, usually containing about 2.5 to about 10 milligrams of apomorphine, have been found to be effective in male patients suffering from psychogenic erectile dysfunction for the induction and maintenance of an erection sufficient for intercourse (i.e., vaginal penetration) without nausea or other undesirable side effects. The apomorphine is administered sublingually, preferably about 15 to about 20 minutes prior to sexual activity, and so as to maintain a predetermined circulating serum levels and mid-brain tissue levels of apomorphine during the period of sexual activity sufficient to induce an erection adequate for vaginal penetration but less than the amount that induces nausea. The plasma concentration of apomorphine should be maintained at no more than about 5.5 nanograms per milliliter, preferably about 0.3 to about 4 nanograms per milliliter, and more preferably about 1 to about 2 nanograms per milliliter.
Apomorphine may be included in a pharmaceutical composition comprising apomorphine and a physiologically tolerable diluent. The present invention includes apomorphine and salts thereof as described above formulated into compositions together with one or more non-toxic physiologically tolerable or acceptable diluents, carriers, adjuvants or vehicles that are collectively referred to herein as diluents for intranasal delivery or for oral administration in solid or liquid form.
These compositions can also contain adjuvants such as preserving, wetting, emulsifying, and dispensing agents. Prevention of the action of microorganisms can be ensured by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, and the like. It may also be desirable to include isotonic agents, for example sugars and sodium chloride, among others.
Suspensions, in addition to the active compounds, may contain suspending agents, as for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, or mixtures of these substances, among others.
Useful intranasal formulations contain a stabilizer and a surfactant. Among the pharmaceutically acceptable surfactants are polyoxyethylene castor oil derivatives, such as polyoxyethylene-glycerol-triricinoleate, also known as polyoxyl 35 castor oil (CREMOPHOR EL), or poloxyl 40 hydrogenated castor oil (CREMOPHOR RH40) both available from BASF Corp.; mono-fatty acid esters of polyoxyethylene (20) sorbitan, such as polyoxyethylene (20) sorbitan monolaurate (TWEEN 80), polyoxyethylene monostearate (TWEEN 60), polyoxyethylene (20) sorbitan monopalmitate (TWEEN 40), or polyoxyethylene 20 sorbitan monolaurate (TWEEN 20) all available from ICI Surfactants of Wilmington, Del.); polyglyceryl esters, such as polyglyceryl oleate; and polyoxyethylated kernel oil (LABRAFIL, available from Gattefosse Corp.) Preferably, the surfactant will be between about 0.01% and 10% by weight of the pharmaceutical composition.
Among the pharmaceutically useful stabilizers are antioxidants such as sodium sulfite, sodium metabisulfite, sodium thiosulfate, sodium formaldehyde sulfoxylate, sulfur dioxide, ascorbic acid, isoascorbic acid, thioglycerol, thioglycolic acid, cysteine hydrochloride, acetyl cysteine, ascorbyl palmitate, hydroquinone, propyl gallate, nordihydroguaiaretic acid, butylated hydroxytoluene, butylated hydroxyanisole, alpha-tocopherol and lecithin. Preferably, the stabilizer will be between about 0.01% and 5% by weight of the pharmaceutical composition.
Chelating agents such as ethylene diamine tetraacetic acid, its derivatives and salts thereof, dihydroxyethyl glycine, citric acid and tartaric acid among others may also be utilized.
Proper fluidity can be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants.
Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound may be mixed with at least one inert, pharmaceutically acceptable excipient or carrier, such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol and silicic acid; b) binders such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and acacia; c) humectants such as glycerol; d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and sodium carbonate; e) solution retarding agents such as paraffin; f) absorption accelerators such as quaternary ammonium compounds; g) wetting agents such as cetyl alcohol and glycerol monostearate; h) absorbents such as kaolin and bentonite clay and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents.
Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like.
The solid dosage forms of tablets, dragees, capsules, pills and granules can be prepared with coatings and shells such as enteric coatings and other coatings well-known in the pharmaceutical formulating art. They may optionally contain opacifying agents and may also be of a composition such that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes.
The active compounds can also be in micro-encapsulated form, if appropriate, with one or more of the above-mentioned excipients.
Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethyl formamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan and mixtures thereof.
Besides inert diluents, the oral compositions may also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring and perfuming agents.
The apomorphine may also be administered in the form of liposomes. As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. Liposomes are formed by mono- or multi-lamellar hydrated liquid crystals which are dispersed in an aqueous medium. Any non-toxic, physiologically acceptable and metabolizable lipid capable of forming liposomes can be used. The present compositions in liposome form can contain, in addition to a compound of the present invention, stabilizers, preservatives, excipients and the like. The preferred lipids are natural and synthetic phospholipids and phosphatidyl cholines (lecithins) used separately or together.
Methods to form liposomes are known in the art. See, for example, Prescott, Ed., Methods in Cell Biology, Volume XIV, Academic Press, New York, N.Y. (1976), p. 33 et seq.
The ability of apomorphine to ameliorate anti-depressant-induced sexual dysfunction is described in detail hereinafter in the Examples. These Examples are presented to describe preferred embodiments and utilities of the invention and are not meant to limit the invention unless otherwise stated in the claims appended hereto.

Treatment of anti-depression drug-induced sexual dysfunction with apomorphine


A cleaning wipe comprising a nonwoven fabric wherein the nonwoven fabric is impregnated with an antibacterial cleaning composition.

The present invention relates to a nonwoven fabric which has been impregnated with an antibacterial liquid cleaning composition.
The patent literature describes numerous wipes for both body cleaning and cleaning of hard surfaces but none describe the instant cleaning wipes which have improved cleaning characteristics in the minimization of streaking and residue.
U.S. Pat. Nos. 5,756,612; 5,763,332; 5,908,707; 5,914,177; 5,980,922 and 6,168,852 teach cleaning compositions which are inverse emulsions.
U.S. Pat. Nos. 6,183,315 and 6,183,763 teach cleaning compositions containing a proton donating agent and having an acidic pH.
U.S. Pat. Nos. 5,863,663; 5,952,043; 6,063,746 and 6,121,165 teaches cleaning compositions which are out in water emulsions.
An antibacterial cleaning wipe for cleaning hard surfaces such as walls, counter tops and floors comprises a nonwoven fabric containing at least polyester fibers and viscose fibers, wherein is the nonwoven fabric is impregnated with a liquid cleaning composition containing at least one nonionic surfactant, a disinfecting agent, a cosurfactant, an alkanol, water and optionally an anionic surfactant and a zwitterionic surfactant, wherein the liquid cleaning composition is not an emulsion and does not contain proteins, metallic salts, enzymes, amides, sodium hypochlorite, dimethicone, N-methyl-2-pyrrolidone, monoalkyl phosphate or silicon based sulfosuccinate.
The present invention relates to an antibacterial cleaning wipe for hard surfaces which comprises approximately:
(a) 20 wt. % to 30 wt. % of a nonwoven fabric which consists of at least polyester fibers and viscose fibers and preferably consists of 60 wt. % to 95 wt. % of wood pulp fibers, 2.5 wt. % to 20 wt. % of viscose fibers and 2.5 wt. % to 20 wt. % of polyester fibers; and
(b) 70 wt. % to 80 wt. % of a liquid cleaning composition being impregnated in said nonwoven fabric, wherein said liquid cleaning composition comprises:
(i) 0.5 wt. % to 8 wt. %, more preferably 1.0 wt. % to 6 wt. % of at least one ethoxylated nonionic surfactant;
(ii) 0.25 wt. % to 10 wt. %, more preferably 0.5 wt. % to 6 wt. % of a C1-C4 alkanol;
(iii) 0.5 wt. % to 8 wt. %, more preferably 1 wt. % to 5 wt. % of a cosurfactant;
(iv) 0 to 15 wt. %, more preferably 0.25 wt. % to 10 wt. % of an anionic surfactant;
(v) 0 to 5 wt. %, more preferably 0.25 wt. % to 4 wt. % of a zwitterionic surfactant;
(vi) 0.1 wt. % to 2 wt. %, more preferably 0.2 wt. % to 1.4 wt. % of a disinfecting agent;
(vii) the balance being water, wherein the composition has a pH of about 5.5 to about 7, more preferably about 5.8 to about 6.6.
The composition can also optionally contain a water-soluble zwitterionic surfactant (betaine), which may be used in the instant cleaning composition, constitutes about 0 to 5%, preferably 0.1% to 5%, by weight and provides good foaming properties and mildness to the composition. The zwitterionic surfactant is a water soluble betaine having the general formula:
wherein Xxe2x88x92 is selected from the group consisting of SO3xe2x88x92 and CO2xe2x88x92 and R1 is an alkyl group having 10 to about 20 carbon atoms, preferably 12 to 16 carbon atoms, or the amido radical:
wherein R is an alkyl group having about 9 to 19 carbon atoms and a is the integer 1 to 4; R2 and R3 are each alkyl groups having 1 to 3 carbons and preferably 1 carbon; R4 is an alkylene or hydroxyalkylene group having from 1 to 4 carbon atoms and, optionally, one hydroxyl group. Typical alkyldimethyl betaines include decyl dimethyl betaine or 2-(N-decyl-N,N-dimethyl-ammonia) acetate, coco dimethyl betaine or 2-(N-coco N,N-dimethylammonia) acetate, myristyl dimethyl betaine, palmityl dimethyl betaine, lauryl dimethyl betaine, cetyl dimethyl betaine, stearyl dimethyl betaine, etc. The amidobetaines similarly include cocoamidoethylbetaine, cocoamidopropyl betaine and the like. A preferred betaine is coco (C8-C18) amidopropyl dimethyl betaine. The disinfecting agent can be a preservative such as formalin, glutaraldehyde, a perfume, an essential oil, tetraalkyl ammonium salt, trialkyl benzyl ammonium salt and triclosan and mixtures thereof.
Suitable essential oils are selected from the group consisting of: Anethole 20/21 natural, Aniseed oil china star, Aniseed oil globe brand, Balsam (Peru), Basil oil (India), Black pepper oil, Black pepper oleoresin 40/20, Bois de Rose (Brazil) FOB, Borneol Flakes (China), Camphor oil, White, Camphor powder synthetic technical, Cananga oil (Java), Cardamom oil, Cassia oil (China), Cedarwood oil (China) BP, Cinnamon bark oil, Cinnamon leaf oil, Citronella oil, Clove bud oil, Clove leaf, Coriander (Russia), Coumarin 69xc2x0 C. (China), Cyclamen Aldehyde, Diphenyl oxide, Ethyl vanilin, Eucalyptol, Eucalyptus oil, Eucalyptus citriodora, Fennel oil, Geranium oil, Ginger oil, Ginger oleoresin (India), White grapefruit oil, Guaiacwood oil, Gurjun balsam, Heliotropin, Isobornyl acetate, Isolongifolene, Juniper berry oil, L-methyl acetate, Lavender oil, Lemon oil, Lemongrass oil, Lime oil distilled, Litsea Cubeba oil, Longifolene, Menthol crystals, Methyl cedryl ketone, Methyl chavicol, Methyl salicylate, Musk ambrette, Musk ketone, Musk xylol, Nutmeg oil, Orange oil, Patchouli oil, Peppermint oil, Phenyl ethyl alcohol, Pimento berry oil, Pimento leaf oil, Rosalin, Sandalwood oil, Sandenol, Sage oil, Clary sage, Sassafras oil, Spearmint oil, Spike lavender, Tagetes, Tea tree oil, Vanilin, Vetyver oil (Java), Wintergreen, Allocimene, Arbanex(trademark), Arbanol(copyright), Bergamot oils, Camphene, Alpha-Campholenic aldehyde, I-Carvone, Cineoles, Citral, Citronellol Terpenes, Alpha-Citronellol, Citronellyl Acetate, Citronellyl Nitrile, Para-Cymene, Dihydroanethole, Dihydrocarveol, d-Dihydrocarvone, Dihydrolinalool, Dihydromyrcene, Dihydromyrcenol, Dihydromyrcenyl Acetate, Dihydroterpineol, Dimethyloctanal, Dimethyloctanol, Dimethyloctanyl Acetate, Estragole, Ethyl-2 Methylbutyrate, Fenchol, Fernlol(trademark), Florilys(trademark), Geraniol, Geranyl Acetate, Geranyl Nitrile, Glidmint(trademark) Mint oils, Glidox(trademark), Grapefruit oils, trans-2-Hexenal, trans-2-Hexenol, cis-3-Hexenyl Isovalerate, cis-3-Hexanyl-2-methylbutyrate, Hexyl Isovalerate, Hexyl-2-methylbutyrate, Hydroxycitronellal, Ionone, Isobornyl Methylether, Linalool, Linalool Oxide, Linalyl Acetate, Menthane Hydroperoxide, I-Methyl Acetate, Methyl Hexyl Ether, Methyl-2-methylbutyrate, 2-Methylbutyl Isovalerate, Myrcene, Nerol, Neryl Acetate, 3-Octanol, 3-Octyl Acetate, Phenyl Ethyl-2-methylbutyrate, Petitgrain oil, cis-Pinane, Pinane Hydroperoxide, Pinanol, Pine Ester, Pine Needle oils, Pine oil, alpha-Pinene, beta-Pinene, alpha-Pinene Oxide, Plinol, Plinyl Acetate, Pseudo Ionone, Rhodinol, Rhodinyl Acetate, Spice oils, alpha-Terpinene, gamma-Terpinene, Terpinene-4-OL, Terpineol, Terpinolene, Terpinyl Acetate, Tetrahydrolinalool, Tetrahydrolinalyl Acetate, Tetrahydromyrcenol, Tetralol(copyright), Tomato oils, Vitalizair, Zestoral(trademark).
As used herein and in the appended claims the term xe2x80x9cperfumexe2x80x9d is used in its ordinary sense to refer to and include any non-water soluble fragrant substance or mixture of substances including natural (i.e., obtained by extraction of flower, herb, blossom or plant), artificial (i.e., mixture of natural oils or oil constituents) and synthetically produced substance) odoriferous substances. Typically, perfumes are complex mixtures of blends of various organic compounds such as alcohols, aldehydes, ethers, aromatic compounds and varying amounts of essential oils (e.g., terpenes) such as from 0% to 80%, usually from 10% to 70% by weight, the essential oils themselves being volatile odoriferous compounds and also serving to dissolve the other components of the perfume.
In the present invention the precise composition of the perfume is of no particular consequence to cleaning performance so long as it meets the criteria of water immiscibility and having a pleasing odor. Naturally, of course, especially for cleaning compositions intended for use in the home, the perfume, as well as all other ingredients, should be cosmetically acceptable, i.e., non-toxic, hypoallergenic, etc. The instant compositions show a marked improvement in ecotoxocity as compared to existing commercial products.
Some typical disinfectant agent useful in the instant compositions are tetra alkyl or trialkyl benzyl ammonium salts which are manufactured by Lonza, S.A. They are: Bardac 2180 (or 2170) which is N-decyl-N-isononyl-N,N-dimethyl ammonium chloride; Bardac 22 which is didecyl dimethyl ammonium chloride; Bardac LF which is N,N-dioctyl-N,N-dimethyl ammonium chloride; Bardac 114 which is a mixture in a ratio of 1:1:1 of N-alkyl-N, N-didecyl-N,N-dimethyl ammonium chloride/N-alkyl-N,N-dimethyl-N-ethyl ammonium chloride; and Barquat MB-50 which is N-alkyl-N,N-dimethyl-N-benzyl ammonium chloride.
Suitable water-soluble non-soap, anionic surfactants used in the instant compositions include those surface-active or detergent compounds which contain an organic hydrophobic group containing generally 8 to 26 carbon atoms and preferably 10 to 18 carbon atoms in their molecular structure and at least one water-solubilizing group selected from the group of sulfonate, sulfate and carboxylate so as to form a water-soluble detergent. Usually, the hydrophobic group will include or comprise a C8-C22 alkyl, alkyl or acyl group. Such surfactants are employed in the form of water-soluble salts and the salt-forming cation usually is selected from the group consisting of sodium, potassium, ammonium, magnesium and mono-, di- or tri-C2-C3 alkanolammonium, with the sodium, magnesium and ammonium cations again being preferred.
Examples of suitable sulfonated anionic surfactants are the well known higher alkyl mononuclear aromatic sulfonates such as the higher alkyl benzene sulfonates containing from 10 to 16 carbon atoms in the higher alkyl group in a straight or branched chain, C8-C15 alkyl toluene sulfonates and C8-C15 alkyl phenol sulfonates.
A preferred sulfonate is linear alkyl benzene sulfonate having a high content of 3- (or higher) phenyl isomers and a correspondingly low content (well below 50%) of 2- (or lower) phenyl isomers, that is, wherein the benzene ring is preferably attached in large part at the 3 or higher (for example, 4, 5, 6 or 7) position of the alkyl group and the content of the isomers in which the benzene ring is attached in the 2 or 1 position is correspondingly low. Particularly preferred materials are set forth in U.S. Pat. No. 3,320,174.
Other suitable anionic surfactants are the olefin sulfonates, including long-chain alkene sulfonates, long-chain hydroxyalkane sulfonates or mixtures of alkene sulfonates and hydroxyalkane sulfonates. These olefin sulfonate detergents may be prepared in a known manner by the reaction of sulfur trioxide (SO3) with long-chain olefins containing 8 to 25, preferably 12 to 21 carbon atoms and having the formula RCHxe2x95x90CHR1 where R is a higher alkyl group of 6 to 23 carbons and R1 is an alkyl group of 1 to 17 carbons or hydrogen to form a mixture of sultones and alkene sulfonic acids which is then treated to convert the sultones to sulfonates. Preferred olefin sulfonates contain from 14 to 16 carbon atoms in the R alkyl group and are obtained by sulfonating an xcex1-olefin.
Other examples of suitable anionic sulfonate surfactants are the paraffin sulfonates containing 10 to 20, preferably 13 to 17, carbon atoms. Primary paraffin sulfonates are made by reacting long-chain alpha olefins and bisulfites and paraffin sulfonates having the sulfonate group distributed along the paraffin chain are shown in U.S. Pat. Nos. 2,503,280; 2,507,088; 3,260,744; 3,372,188; and German Patent 735,096.
Examples of satisfactory anionic sulfate surfactants are the C8-C18 alkyl sulfate salts and the C8-C18 alkyl sulfate salts and the C8-C18 alkyl ether polyethenoxy sulfate salts having the formula R(OC2H4)n OSO3M wherein n is 1 to 12, preferably 1 to 5, and M is a metal cation selected from the group consisting of sodium, potassium, ammonium, magnesium and mono-, di- and triethanol ammonium ions. The alkyl sulfates may be obtained by sulfating the alcohols obtained by reducing glycerides of coconut oil or tallow or mixtures thereof and neutralizing the resultant product.
On the other hand, the alkyl ether polyethenoxy sulfates are obtained by sulfating the condensation product of ethylene oxide with a C8-C18 alkanol and neutralizing the resultant product. The alkyl sulfates may be obtained by sulfating the alcohols obtained by reducing glycerides of coconut oil or tallow or mixtures thereof and neutralizing the resultant product. On the other hand, the alkyl ether polyethenoxy sulfates are obtained by sulfating the condensation product of ethylene oxide with a C8-C18 alkanol and neutralizing the resultant product. The alkyl ether polyethenoxy sulfates differ from one another in the number of moles of ethylene oxide reacted with one mole of alkanol. Preferred alkyl sulfates and preferred alkyl ether polyethenoxy sulfates contain 10 to 16 carbon atoms in the alkyl group.
The C8-C12 alkylphenyl ether polyethenoxy sulfates containing from 2 to 6 moles of ethylene oxide in the molecule also are suitable for use in the inventive compositions. These surfactants can be prepared by reacting an alkyl phenol with 2 to 6 moles of ethylene oxide and sulfating and neutralizing the resultant ethoxylated alkylphenol.
Other suitable anionic surfactants are the C9-C15 alkyl ether polyethenoxyl carboxylates having the structural formula R(OC2H4)nOX COOH wherein n is a number from 4 to 12, preferably 5 to 10 and X is selected from the group consisting of
CH2, (C(O)R1 and
wherein R1 is a C1-C3 alkylene group. Preferred compounds include C9-C11 alkyl ether polyethenoxy (7-9) C(O) CH2CH2COOH, C13-C15 alkyl ether polyethenoxy (7-9)
and C10-C12 alkyl ether polyethenoxy (5-7) CH2COOH. These compounds may be prepared by considering ethylene oxide with appropriate alkanol and reacting this reaction product with chloracetic acid to make the ether carboxylic acids as shown in U.S. Pat. No. 3,741,911 or with succinic anhydride or phthalic anhydride. Obviously, these anionic surfactants will be present either in acid form or salt form depending upon the pH of the final composition, with salt forming cation being the same as for the other anionic surfactants.
The water soluble nonionic surfactants utilized in this invention are commercially well known and include the primary aliphatic alcohol ethoxylates, secondary aliphatic alcohol ethoxylates, alkylphenol ethoxylates and ethylene-oxide-propylene oxide condensates on primary alkanols, such a Plurafacs (BASF) and condensates of ethylene oxide with sorbitan fatty acid esters such as the Tweens (ICI). The nonionic synthetic organic detergents generally are the condensation products of an organic aliphatic or alkyl aromatic hydrophobic compound and hydrophilic ethylene oxide groups. Practically any hydrophobic compound having a carboxy, hydroxy, amido, or amino group with a free hydrogen attached to the nitrogen can be condensed with ethylene oxide or with the polyhydration product thereof, polyethylene glycol, to form a water-soluble nonionic detergent. Further, the length of the polyethenoxy chain can be adjusted to achieve the desired balance between the hydrophobic and hydrophilic elements.
The nonionic detergent class includes the condensation products of a higher alcohol (e.g., an alkanol containing about 8 to 18 carbon atoms in a straight or branched chain configuration) condensed with about 5 to 30 moles of ethylene oxide, for example, lauryl or myristyl alcohol condensed with about 16 moles of ethylene oxide (EO), tridecanol condensed with about 6 to moles of EO, myristyl alcohol condensed with about 10 moles of EO per mole of myristyl alcohol, the condensation product of EO with a cut of coconut fatty alcohol containing a mixture of fatty alcohols with alkyl chains varying from 10 to about 14 carbon atoms in length and wherein the condensate contains either about 6 moles of EO per mole of total alcohol or about 9 moles of EO per mole of alcohol and tallow alcohol ethoxylates containing 6 EO to 11 EO per mole of alcohol.
A preferred group of the foregoing nonionic surfactants are the Neodol ethoxylates (Shell Co.), which are higher aliphatic, primary alcohol containing about 9-15 carbon atoms, such as C9-C11 alkanol condensed with 2.5 to 10 moles of ethylene oxide (NEODOL 91-2.5 or -5 or-6 or -8), C12-13 alkanol condensed with 6.5 moles ethylene oxide (Neodol 23-6.5), C12-15 alkanol condensed with 12 moles ethylene oxide (Neodol 25-12), C14-15 alkanol condensed with 13 moles ethylene oxide (Neodol 45-13), and the like.
An especially preferred nonionic system comprises the mixture of a nonionic surfactant formed from a C9-C11 alkanol condensed with 2 to 3.5 moles of ethylene oxide (C9-11 alcohol EO 2 to 3.5:1) with a nonionic surfactant formed from a C9-C11 alkanol condensed with 7 to 9 moles of ethylene oxide (C9-C11 alcohol EO 7 to 9:1), wherein the weight ratio of the C9-C11 alcohol EO 7 to 9:1 to the C9-C11 alcohol EO 2 to 3.5:1 is from 8:1 to 1:1 from preferably 6:1 to 3:1.
Additional satisfactory water soluble alcohol ethylene oxide condensates are the condensation products of a secondary aliphatic alcohol containing 8 to 18 carbon atoms in a straight or branched chain configuration condensed with 5 to 30 moles of ethylene oxide. Examples of commercially available nonionic detergents of the foregoing type are C11-C15 secondary alkanol condensed with either 9 EO (Tergitol 15-S-9) or 12 EO (Tergitol 15-S-12) marketed by Union Carbide.
Other suitable nonionic detergents include the polyethylene oxide condensates of one mole of alkyl phenol containing from about 8 to 18 carbon atoms in a straight- or branched chain alkyl group with about 5 to 30 moles of ethylene oxide. Specific examples of alkyl phenol ethoxylates include nonyl phenol condensed with about 9.5 moles of EO per mole of nonyl phenol, dinonyl phenol condensed with about 12 moles of EO per mole of phenol, dinonyl phenol condensed with about 15 moles of EO per mole of phenol and di-isoctylphenol condensed with about 15 moles of EO per mole of phenol. Commercially available nonionic surfactants of this type include Igepal CO-630 (nonyl phenol ethoxylate) marketed by GAF Corporation.
Also among the satisfactory nonionic detergents are the water-soluble condensation products of a C8-C20 alkanol with a heteric mixture of ethylene oxide and propylene oxide wherein the weight ratio of ethylene oxide to propylene oxide is from 2.5:1 to 4:1, preferably 2.8:1 to 3.3:1, with the total of the ethylene oxide and propylene oxide (including the terminal ethanol or propanol group) being from 60-85%, preferably 70-80%, by weight. Such detergents are commercially available from BASF-Wyandotte and a particularly preferred detergent is a C10-C16 alkanol condensate with ethylene oxide and propylene oxide, the weight ratio of ethylene oxide to propylene oxide being 3:1 and the total alkoxy content being about 75% by weight.
Condensates of 2 to 30 moles of ethylene oxide with sorbitan mono- and tri-C10-C20 alkanoic acid esters having a HLB of 8 to 15 also may be employed as the nonionic detergent ingredient in the described composition. These surfactants are well known and are available from Imperial Chemical Industries under the Tween trade name. Suitable surfactants include polyoxyethylene (4) sorbitan monolaurate, polyoxyethylene (4) sorbitan monostearate, polyoxyethylene (20) sorbitan trioleate and polyoxyethylene (20) sorbitan tristearate.
Other suitable water-soluble nonionic detergents are marketed under the trade name xe2x80x9cPluronicsxe2x80x9d. The compounds are formed by condensing ethylene oxide with a hydrophobic base formed by the condensation of propylene oxide with propylene glycol. The molecular weight of the hydrophobic portion of the molecule is of the order of 950 to 4000 and preferably 200 to 2,500. The addition of polyoxyethylene radicals to the hydrophobic portion tends to increase the solubility of the molecule as a whole so as to make the surfactant water-soluble. The molecular weight of the block polymers varies from 1,000 to 15,000 and the polyethylene oxide content may comprise 20% to 80% by weight. Preferably, these surfactants will be in liquid form and satisfactory surfactants are available as grades L 62 and L 64.
The cosurfactants in the instant compositions are selected from the group consisting of polypropylene glycol of the formula HO(CH3CHCH2O)nH wherein n is a number from 1 to 18, and mono and di C1-C6 alkyl ethers and esters of ethylene glycol and propylene glycol having the structural formulas R(X)nOH, R1(X)nOH, R(X)nOR and R1(X)nOR1 wherein R is C1-C6 alkyl group, R1 is C2-C4 acyl group, X is (OCH2CH2) or (OCH2(CH3)CH) and n is a number from 1 to 4, diethylene glycol, triethylene glycol, an alkyl lactate, wherein the alkyl group has 1 to 6 carbon atoms, 1methoxy-2-propanol, 1methoxy-3-propanol, and 1methoxy 2-, 3- or 4-butanol.
Representative members of the polypropylene glycol include dipropylene glycol and polypropylene glycol having a molecular weight of 150 to 1000, e.g., polypropylene glycol 400. Satisfactory glycol ethers are ethylene glycol monobutyl ether (butyl cellosolve), diethylene glycol monobutyl ether (butyl carbitol), triethylene glycol monobutyl ether, mono, di, tri propylene glycol monobutyl ether, tetraethylene glycol monobutyl ether, mono, di, tripropylene glycol monomethyl ether, propylene glycol monomethyl ether, ethylene glycol monohexyl ether, diethylene glycol monohexyl ether, propylene glycol tertiary butyl ether, ethylene glycol monoethyl ether, ethylene glycol monomethyl ether, ethylene glycol monopropyl ether, ethylene glycol monopentyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, diethylene glycol monopentyl ether, triethylene glycol monomethyl ether, triethylene glycol monoethyl ether, triethylene glycol monopropyl ether, triethylene glycol monopentyl ether, triethylene glycol monohexyl ether, mono, di, tripropylene glycol monoethyl ether, mono, di tripropylene glycol monopropyl ether, mono, di, tripropylene glycol monopentyl ether, mono, di, tripropylene glycol monohexyl ether, mono, di, tributylene glycol mono methyl ether, mono, di, tributylene glycol monoethyl ether, mono, di, tributylene glycol monopropyl ether, mono, di, tributylene glycol monobutyl ether, mono, di, tributylene glycol monopentyl ether and mono, di, tributylene glycol monohexyl ether, ethylene glycol monoacetate and dipropylene glycol propionate. While all of the aforementioned glycol ether compounds provide the described stability, the most preferred cosurfactant is propylene glycol N-butyl ether.
The preferred C1-C4 alkanols are ethanol or isopropanol and mixtures thereof.
The final essential ingredient in the instant composition is water. The proportion of water in the compositions generally is in the range of 70 wt. % to 98.5 wt. %.
The cleaning composition of this invention may, if desired, also contain other components either to provide additional effect or to make the product more attractive to the consumer. The following are mentioned by way of example: Colors or dyes in amounts up to 0.5% by weight; preservatives with a specific activity spectrum such as iodo propynyl butyl carbamate, 5-bromo-5-nitro-dioxan-1,3; 5-chloro-2-methyl-4-isothaliazolin-3-one, etc., in amounts up to 0.5% by weight; antioxidizing agents such as 2.6-di-ter.butyl-p-cresol in amounts up to 0.5% by weight; and pH adjusting agents, such as citric acid, sulfuric acid or sodium hydroxide, mono-, di- and tri-alkanol amines as needed.
The cleaning compositions are prepared by simple batch mixing at 25xc2x0 C.-30xc2x0 C. The nonwoven fabric is impregnated with the liquid cleaning composition by means of a positive impregnation process. The liquid is positively fed into the nonwoven fabric through a controlled gear pump and injection bar at a ratio of about 2 grams of liquid cleaning composition to about 1 gram of the nonwoven fabric.
The nonwoven fabric is formed from 10 wt. % to 90 wt. % of viscose fibers and 10 wt. % to 90 wt. % of polyester fibers such as Spunlace made by the Dexter Corporation. More preferably the nonwoven fabric comprises 10 wt. % to 95 wt. % of wood pulp fibers, 1 wt. % to 40 wt. % of viscose fibers and 1 wt. % to 40 wt. % of polyester fibers. Such a nonwoven fabric which is manufactured by Dexter Corporation under the name Hydraspun comprises about 60% to 95% of wood pulp fabrics, 2.5 wt. % to 20 wt. % of viscose fibers and 2.5 wt. % to 20 wt. % of polyester fibers.

Antibacterial cleaning wipe comprising triclosan


The invention relates to protective colloid-stabilized copolymerizate latex particles with a heterogeneous morphology based on a vinyl acetate-ethylene copolymerizate and optionally further monomers, the latex particles having an ethylene content of less than 30 wt. %, based oh the total monomer quantity, comprising an outer phase with a polymer of vinyl acetate and approximately 0 to 40 wt. % ethylene, based on the monomers of the outer phase, and an inner phase with a polymer of vinyl acetate and approximately 0 to 40 wt. % ethylene; based on the monomers of the inner phase and in which at least one of the two phases contains ethylene. The invention also relates to a process for the preparation of acqueous dispersions of copolymerizate latex particles with heterogeneous morphology and the use thereof. The invention is characterized in that the heterogeneous morphology can be obtained in a planned manner, i.e. whether there is a core-shell or inverse core-shell morphology and the composition of the inner and the outer phases can also be varied in flexible manner within the indicated ranges.

The invention relates to protective colloid-stabilized copolymerizate latex particles with heterogeneous morphology based on a vinyl acetate-ethylene copolymerizate, processes for the production thereof and the use thereof.
For some time now copolymerizates in the form of stabilized, aqueous polymerizate dispersions (latices) or preferably as redispersible powders have been increasingly used for modifying mineral building materials. As a result of such additives the characteristics profiles of mineral building materials, such as mortar, concrete, etc. can be controlled in a planned manner and the copolymerizates can be based on the most varied monomers. The modifying action is based less on the chemical characteristics of the copolymerizate used than on its physical characteristics. In particular, copolymerizates based on the monomers vinyl acetate and ethylene have particular advantages as modifying additives in the building sector,for hydraulically setting systems.
The production of so-called heterogeneous latex morphologies is of interest in this connection. Due to their molecular structure such latex particles have special characteristics, which not only permit their universal use, but also a more planned setting of the desired characteristics. In this heterogeneous structure of the latex particles, a distinction is in each case made between a relatively hydrophobic and a relatively hydrophilic area. For thermodynamic equilibrium reasons, under normal conditions there is frequently a hydrophilic shell (outer phase) and a hydrophobic core (inner phase), because this structure can generally be more easily produced by a conventional emulsion polymerization. However, it is much more difficult to produce systems having a so-called inverse core-shell structure, in which firstly the shell and then the core are produced. This is more particularly the case when performing so-called pressure polymerizations, if e.g. ethylene is used.
Please note that the core-shell morphology as described herein, is not a stabilized latex particle known in the art, wherein a protective colloid or surfactant is arranged on the surface of the polymer particle to stabilize it in an additional phase. In contrary, the polymer particle itself should be structured in the present invention, i.e. should have a heterogeneous morphology.
Apart from aqueous polymer dispersions, a further very appropriate application form of the polymer additive acting in a modifying manner is a redispersible powder available from such dispersions by drying. These powders are, due to their easy handling, easier, space-saving transportation, easier dosability and less expensive storage, very advantageous. Due to the readily available dispersing medium xe2x80x9cwaterxe2x80x9d, the powder form is also desired in this respect.
The prior art provides numerous publications dealing with vinyl acetate-ethylene copolymers and which in part would result in redispersible powders. For example, EP 444 827 A1 describes copolymer particles with a core-shell structure, in which the Tg-value is in the range 0 to xe2x88x9230xc2x0 C. and the core, apart from 10 to 30 wt. % alkylene and 1 to 10 wt. % alkylacrylate, also contains 10 to 60 wt. % vinyl alkanoate, 10 to 40 wt. % vinyl esters having a specific chemical formula and 0.1 to 5 wt. % vinyl silane. The particles are used in the form of copolymer emulsions for pigmented surface coatings.
However, a dispersible powder is not described.
The 1969 DE-OS 2 055 978 relates to the preparation of a water-based gloss paint, which contains a vinyl acetate-ethylene copolymerizate as the binder. The copolymerizate is produced by (1) preparing an aqueous polymerization starting medium with water, catalyst and a small amount of vinyl acetate, (2) polymerizing the vinyl acetate, (3) introducing ethylene into the reaction mixture in order to obtain a pressure in the range 3.5 to 105 atxc3xc, as well as the gradual addition of vinyl acetate and an acrylamide and polymerizing both monomers in the presence of the previously formed polyvinyl acetate at a temperature of 40 to 90xc2x0 C., (4) releasing the overpressure, (5) adding a water-soluble emulsifier and a small amount of an alkyl acrylate and (6) polymerizing the alkyl acrylate in the presence of the polymer dispersion obtained. A surfactant can optionally be present in the first polymerization stage. However, this cannot produce a heterogeneous morphology. In addition, only dispersions, but not redispersible powders are described.
According to the disclosure of EP 757 065 A3 a protective colloid-stabilized copolymerizate is prepared, which has a glass transition temperature of xe2x88x9240xc2x0 C. to 10xc2x0 C., as well as an ethylene content of at least 30 wt. %, based on the total quantity of the monomers, the heterogeneous structure of the copolymer particles containing a first copolymerizate phase with vinyl acetate and  greater than 40 wt. % ethylene, based on the total monomer quantity in this phase and a final copolymerizate phase with vinyl acetate and 5 to 40 wt. % ethylene, based on the total monomer quantity in this phase.
The process for the production of this copolymerizate is based on the polymerization of vinyl acetate and ethylene and optionally further comonomers, part of the monomers undergoes radical copolymerization at an ethylene pressure of 55 to 150 bar in the presence of a protective colloid, optionally further monomers are polymerized and then, under an ethylene pressure between 1 and 55 bar, further radical copolymerization takes place. The copolymerizates described are used in the form of dispersions or redispersible powders as binders in building materials or sealing sludges.
The problem of the invention is to further develop the previously described vinyl acetate-ethylene copolymerizate latex particles or the aqueous dispersions obtained in such a way that, whilst retaining advantageous characteristics, or in individual cases even better characteristics, a heterogeneous morphology is obtained in the latex particles. In addition, the copolymerizate latex particles are to be improved in that in their final applications, such as e.g. in plastics-containing, cement-bonded systems, due to the desirable successive reactions, they lead to improved use products. Apart from the aqueous dispersions, redispersible powders are to be accessible, which substantially maintain their advantageous characteristics following redispersion in the aqueous medium. In addition, a process is to be provided, which permits the planned setting and modification of the heterogeneous morphology of latex particles, also when performing a pressure emulsion polymerization.
According to the invention, this problem is solved by protective colloid-stabilized copolymerizate latex particles with a heterogeneous morphology based on a vinyl acetate-ethylene copolymerizate and optionally further monomers, the latex particles having an ethylene content of less than 30 wt. %, based on the total monomer quantity, comprising an outer phase with a polymer of vinyl acetate and approximately 0 to 40 wt. % ethylene, based on the monomers of the outer phase, and an inner phase with a polymer of vinyl acetate and approximately 0 to 40 wt. % ethylene, based on the monomers of the inner phase and in which at least one of the two phases contains ethylene.
Copolymer latex particles with heterogeneous morphology and a total ethylene content of less than 30 wt. %, based on the total monomer quantity are made available, the ethylene content in the individual phases being in the range approximately 0 to 40 wt. %, based on the monomers of the particular phase. A polymer with ethylene content need not simultaneously be present in both phases and instead, for bringing about the characteristics according to the invention, it is sufficient if one of the two phases only contains a vinyl acetate homopolymer, optionally a vinyl acetate copolymer without ethylene.
It is important for solving the aforementioned set problem for the indicated weight quantities to be maintained. In particular, based on the total monomer quantity, the ethylene content must be below 30 wt. %. Preferably the ethylene content is between approximately 2 and 30 and in particularly preferred manner between approximately 5 and 25 wt. %, based on the total monomer quantity.
Through the choice and quantity of the monomers used, i.e. vinyl acetate, ethylene and optionally further monomers, the desired characteristics can be set in a planned manner. For example, the glass transition temperature Tg of the copolymerizate latex particles according to the invention can be varied. The weight proportions of the different monomers is in simple manner chosen in such a way that the glass transition temperature Tg (mid-point temperature according to ASTM D 3418-82) of the film formation of the latex particles to be used correspondingly has the modifying action, a range of xe2x88x9270 to +110xc2x0 C. being possible. The glass transition temperature can e.g. be measured by DSC methods or determined theoretically by calculation in accordance with the Fox equation (T. G. Fox, Bull. Am. Phy. Soc. (ser II), 1, 123 (1956) and Ullmann""s Enzyklopadie der Technischen Chemie, vol. 19, 4th edition, Verlag Chemie, Weinheim, 1980, pp 17/18). In the present invention the glass transition temperatures are determined by differential scanning calorimetry (DSC).
Preferably, in the protective colloid-stabilized copolymerizate latex particles according to the invention, the outer and inner phases have different glass transition temperatures Tg. In particular, the harder phase, i.e. the hydrophilic phase, has a glass transition temperature Tg of approximately 20 to 35xc2x0 C. and the softer or hydrophobic phase a Tg of approximately xe2x88x9240 to +20xc2x0 C.
According to a preferred embodiment, the weight ratio of the inner to the outer phase is between 95:5 and 5:95, particularly between approximately 75:25 and approximately 40:60. By setting the weight ratio of the inner to the outer phase it is also possible to influence the characteristics to be obtained. For example, in a copolymerizate latex particle an outer phase essentially formed from vinyl acetate monomers in the applications envisaged leads to a better adhesion, e.g. to wood.
Further monomers may optionally be present in one or both phases besides ethylene and vinyl acetate monomers. There are no restrictions within the scope of the invention concerning the choice of monomers. The further monomers can be in the form of aliphatic vinyl (C3-C20)-carboxylic esters, (C1-C20)-acrylic esters, methacrylic esters, optionally substituted with epoxy and/or hydroxyl groups, maleic diesters of aliphatic (C1-C20)-alcohols, sulphonate or sulphonic acid group-carrying monomers, xcex1,xcex2-unsaturated carboxylic acids, N-methylol group-carrying monomers, (C1-C20)-alkenyl (meth)acrylic esters, cationic monomers, crosslinking monomers in the form of radical reacting di- and/or triolefins. This list is not exhaustive and the expert is aware of further copolymerizable monomers which are suitable here.
Additionally at least one ionic monomer is preferably contained in the outer phase. This leads to a rise in the hydrophilicity of this phase. The term xe2x80x9cionic monomerxe2x80x9d is not particularly restricted, provided that it is a monomer with one or more positive or negative functionalities in the molecule. These are e.g. monomers with cationic functionality, such as are attributed to a quaternary ammonium group or having an anionic functionality, such as sulphonates, sulphates, particularly carboxylic acids and their derivatives. The ionic monomer is preferably present in a quantity of approximately 0.2 to 10.0 wt. %, based on the total monomer quantity of the particular phase.
In order to bring about a stabilization of the heterogeneous morphology in the vinyl acetate-ethylene latex particles according to the invention, additional monomers with crosslinking reactivity can be present. These can be known, crosslinking monomers, such as e.g. vinyl (meth)acrylates, divinyl adipates, allyl (meth)acrylates, diallylphthalates, triallylcyanurates, ethylene glycol di(meth)acrylates, butane diol di(meth)acrylates and hexane diol di(meth)acrylates.
The vinyl acetate-ethylene latex particles with heterogeneous morphology can be present both in the form of aqueous dispersions and in the form of redispersible powders through a corresponding removal of the water. An appropriate form for the intended use can always be chosen.
The invention also relates to a process for the production of aqueous dispersions of copolymer latex particles with heterogeneous morphology by copolymerizing monomers in the form of ethylene, vinyl acetate and optionally further monomers, whilst incorporating protective colloids, initiators and optionally surfactants, comprising the following stages:
(1) emulsion polymerization of vinyl acetate in the presence of protective colloids, initiators and optionally surfactants, optionally in the presence of ethylene and in the case of ethylene addition the ethylene pressure is set below 50 bar and
(2) continued emulsion polymerization with vinyl acetate by (a) adding ethylene in a quantity such that the ethylene pressure rises to above approximately 60 bar or (b) addition of an ionic monomer and optionally ethylene.
This process permits the planned setting of the heterogeneous morphology of the copolymerizate latex particles according to the invention through precisely respecting the above parameters. In stage (1) vinyl acetate is emulsion polymerized in the presence of protective colloids, initiators and optionally surfactants, optionally accompanied by the supply of ethylene and when ethylene is added the ethylene pressure is always kept below 50 bar. This ethylene pressure of 50 bar is a critical value and must be maintained in order to obtain the desired heterogeneous morphology.
The emulsion polymerization of vinyl acetate and optionally present ethylene is carried out accompanied by the addition of protective colloids and optionally surfactants, such as emulsifiers, as stabilizers. The stabilizers in the form of protective colloids and/or emulsifiers selectable according to the invention is subject to no restrictions. Emulsifiers usable according to the invention are nonionic emulsifiers, such as e.g. alkyl alcohol DE 15 or 25 (DE=degree of ethoxylation), particularly C13-alcohol DE 15 or 25, alkyl phenol DE 10 or 50, particularly nonyl phenol DE 10 or 50, sorbitan fatty acid esters, ethoxylated fatty acid esters, glycerol fatty acid esters, ethoxylated alkyl amines; anionic emulsifiers, such as ammonium, sodium or calcium salts of various fatty acids, alkyl aryl sulphonic acids, alkyl sulphonates, alkyl ether sulphates, alkyl sulphate esters, ethoxylated alkyl ether sulphonates, ethoxylated alkyl allyl ether sulphonates, alkyl phenol ether sulphates, dialkyl sulphosuccinates and cationic emulsifiers, such as in particular alkyl ammonium acetate, quaternary ammonium group-containing compounds and pyridinium compounds.
As protective colloids use can be e.g. be made of polyethylene oxide, starch and starch derivatives, gelatin, casein and other water-soluble proteins, water-soluble cellulose derivatives, such as hydroxyethyl cellulose, polysaccharides, water-soluble polyacrylates, such as acrylic acid copolymerizates, ethylene oxide-propylene oxide block copolymer, polyvinyl alcohol and/or polyvinyl pyrrolidone and functionalized polyvinyl alcohols, such as acetoacetolyzed polyvinyl alcohol. Suitable protective colloids are also described in Houben-Weyl, Methoden der organischen Chemie, vol. XIV/1, Makromolekulare Stoffe, Georg Thieme Verlag, Stuttgart, 1961, pp 411-420. Particularly preferred protective colloids in the present invention are polyvinyl alcohol, cellulose derivatives, starch derivatives and/or polyvinyl pyrrolidone, polyvinyl alcohol being particularly preferred. It can be used in partly hydrolyzed form, i.e. with different polyvinyl acetate contents in the range of approximately 5 to 20%. The monomer used in stage (1) can also be grafted onto the protective colloid, although this is not absolutely necessary. In a preferred embodiment the protective colloid is used in a quantity of approximately 2.0 to 20 wt. %, based on the total monomer quantity.
It is pointed out that ethylene need not be present in stage (1), so that the phase resulting from stage (1) can essentially only be built up of vinyl acetate and optionally further monomers. If ethylene is additionally added, it is vital to maintain the ethylene pressure below 50 bar and preferably between approximately 10 and approximately 49 bar. If ethylene is used in stage (1) there are preferably approximately 0.01 to 0.5 parts by weight ethylene for 1 part by weight vinyl acetate.
In the following stage (2) two alternative process variants are possible. Through the choice of one of the two variants it is possible in planned manner either to perform a core-shell or an inverse core-shell polymerization. According to variant (a) ethylene is added in a quantity such that at the start of addition the ethylene pressure is set at above approximately 60 bar. However, this does not mean that the ethylene pressure throughout the emulsion polymerization in stage (2) is kept at or in the range of this value. Following the initial ethylene addition with an addition pressure of over approximately 60 bar, the ethylene pressure continuously drops, because the ethylene supplied is consumed by the polymerization process. Working preferably takes place in stage (2) under an ethylene initial pressure of approximately 61 to approximately 125 bar. If the polymer produced in stage (1) is grafted on the protective colloid, with said inventive variant an inverse core-shell polymerization is performed, i.e. the phase resulting from stage (1) is the outer phase in the vinyl acetate-ethylene latex particles obtained and the phase resulting from stage (2), variant (a) always becomes the inner phase of the vinyl acetate-ethylene latex particles.
If in the inventive process variant (b) is chosen, emulsion polymerization is continued accompanied by the addition of one or more ionic monomers and optionally additional ethylene. If stage (1), as described hereinbefore, is followed by variant (2) (b), a core-shell polymerization is performed. This means that the phase produced in stage (1) becomes the inner phase and the phase produced in stage (2) (b) becomes the outer phase. If an ionic monomer is used, then the outer phase is always the hydrophilic phase.
Thus, not only can the ethylene and vinyl acetate content of the individual phases be set in variable manner in the indicated ranges, but by the choice of the described process conditions it is possible in planned manner to produce the desired heterogeneous morphology of the copolymerizate latex particles according to the invention.
Emulsion polymerization can also take place using a seed latex, which can be present in a quantity of approximately 0.1 to 20 wt. %, based on the total monomer weight. In said so-called seed polymerization, which is particularly suitable for producing monodisperse latices, a latex with a uniform particle size is firstly introduced. The monomers to be polymerized are dosed into said seed latex in the monomer feed procedure. Polymerization is performed in such a way that the initial latex particles increase in volume, whilst maintaining the monodispersity of the system, but do not increase in numbers. The number of particles is proportional to the quantity initially introduced and a narrow particle size distribution is obtained.
Fundamentally, the process according to the invention can be performed continuously, semicontinuously or as a batch process. It is also clear that for performing the process of the invention account must be taken of the fundamental aspects of an emulsion polymerization. Thus, e.g. radical initiators are used for performing the polymerization. No relevant limitations exist in the present invention when choosing initiators. The radical initiators used according to the invention are either water-soluble or monomer-soluble. Suitable water-soluble initiators are sodium, potassium and ammonium peroxodisulphate, hydrogen peroxide and water-soluble azo compounds such as 2,2xe2x80x2-azobis(2, -amidinopropane dihydrochloride), 2,2xe2x80x2-azobis [2-methyl-N-(2-hydroxethyl)-propionamide] and 2,2xe2x80x2-azobis[2-(2-imidazoline-2-yl)- propane]-dihydrochloride. Suitable monomer-soluble initiators are organic hydroperoxides, such as tert butyl hydroperoxide, pinane hydroperoxide, p-menthane hydroperoxide, cumene hydroperoxide and diisopropyl phenyl hydroperoxide, organic peroxide such as dibenzoyl peroxide, dilauryl peroxide and diacetyl peroxide, as well as monomer-soluble azo compounds, such as azoisobutyronitrile. Mixtures of initiators can also be used.
In place of a radical initiator, it is also possible to use an initiator system formed from a radical initiator of the above-described type and a water-soluble reducing agent. The actual radical initiator is consequently formed during polymerization, which can e.g. take place by thermal decomposition of the above initiator, or by reacting the initiator with an aqueous reducing agent. The water-soluble reducing agents act as activators for the initiators. Suitable reducing agents are ascorbic acid, sodium, potassium and ammonium sulphite, bisulphite and metabisulphite, sodium formaldehyde sulphoxylate, tartaric acid, citric acid and glucose. They can be used in combination with a heavy metal salt. The reducing agents are generally used in a quantity of 0.01 to 2 wt. %, based on the total monomers added. They are generally dosed in during polymerization. The initiators or initiator combinations are generally used in a quantity of 0.01 to 2 wt. %, based on the total monomers. Particular preference is given to sodium, potassium and ammonium persulphate, hydrogen peroxide and tert butyl hydroperoxide combined with a reducing agent, e.g. sodium formaldehyde sulphoxylate or sodium bisulphite.
As a function of the use conditions, conventional additives can be concomitantly used. Examples are thickeners, pigments, flameproofness-increasing materials, fillers, reinforcing agents, film forming aids, antioxidants, fungicides, foam inhibitors, plasticizers, preservatives, wetting agents, rheology modifying agents, resins, adhesion aids, antiblocking agents, etc., which can be added in conventional quantities.
According to the invention, dispersion preparation can also take place without emulsifier addition and optionally a small amount of emulsifier can be used. The proportion of the emulsifier used is appropriately approximately 0.2 to 3 wt. %.
Polymerization is preferably performed between approximately 40 and 100xc2x0 C., particularly between approximately 60 and 90xc2x0 C. The temperature can e.g. depend on the initiator system used. In individual cases the starting temperature is preferably approximately 70xc2x0 C. The evolution of heat due to the exothermic reaction during polymerization can be used for setting the reaction temperature between 80 and 90xc2x0 C. and optionally cooling may be required so as not to exceed the indicated temperature range. It is also possible to remove all the quantity of heat produced, in order to maintain or even drop below the initial temperature of approximately 70xc2x0 C. during the reaction. In individual cases working can take place in an autoclave, which gives a possibility to perform polymerization at above 100xc2x0 C. Preferably in stage (1) the temperature is approximately 40 to 100xc2x0 C. and in stage (2) approximately 60 to 100xc2x0 C.
Apart from the dispersions produced according to the invention, the vinyl acetate-ethylene latex particles with heterogeneous morphology can also be present in the form of a redispersible powder, obtainable by corresponding water removal from the above-described aqueous dispersions. The removal of the water, i.e. the drying of the dispersion, more particularly takes place by spray or freeze drying. A particularly favourable process for drying the aqueous dispersions is the spray drying process, in which the aqueous dispersion is sprayed into a hot air flow and dewatered. Preferably the drying air and the sprayed, aqueous dispersion flow in the same direction through the dryer. The redispersible powder can be used as a finished, pulverulent mixture, which only has to be mixed with water. As a function of the intended use, the powder can be redispersed in the water or in a more or less concentrated form.
The vinyl acetate-ethylene latex particles with heterogeneous morphology in the form of an aqueous dispersion or a redispersible powder according to the present invention have numerous possible uses, e.g. in composite and coating mortars, cement paints and plastics, plastics-containing, cement-bonded systems, particularly in mortars, and plastics-bonded, cement-free binders, particularly in cement-free mortars, gypsum mortars, primers, plasters, carpet, wood, powder and floor adhesives, as well as in wallpaper pastes, disperse powder dyes and glass fibre composite systems. The aqueous dispersions according to the invention and the latex particles obtainable from them by drying, particularly in the form of redispersible powders, are preferably suitable for modifying cement building adhesives, particularly for improving the processability and for increasing the waterproofness. Apart from a preferred use in tile adhesives, the use in cement-containing products of a general nature is important.
The invention leads to numerous advantages. The latex particles according to the invention are characterized by a very flexible, variable composition with respect to the vinyl acetate and ethylene monomers and virtually random ratios can be set within the limits of the described ethylene content. The heterogeneous morphology, i.e. which phase serves as the outer phase and which serves as the inner phase in the ethylene-vinyl acetate latex particles obtained, can be set by the choice of the process parameters. This makes it possible to influence in planned manner the desired characteristics of the latex particles with heterogeneous morphology or to modify them in a planned manner. This permits a control of the characteristics profiles of the substrates to be modified through the improved action of the added particles. In the end products are obtained very favourable characteristics, such as improved processability, better setting behaviour (adhesion), good water resistance and higher storage stability. Thus, both the product implementation and handlability are significantly improved compared with other, heterogeneous vinyl acetate-ethylene latex structures, so that the products produced according to the invention are far superior to conventional, prior art products. The inventively modifiable latex morphology consequently leads to surprising characteristics of the latex particles.
The invention is described in greater detail hereinafter relative to examples, which are not intended to restrict the teaching according to the invention. Within the inventive disclosure, further embodiments are clearly possible.

Latex particles based on a vinyl acetate ethylene copolymerizate processes for the production thereof and the use thereof

National Starch and Chemical Investment Holding Corporation


Mammalian hair growth is reduced by applying to the skin a composition including an inhibitor of an enzyme involved in arachidonic acid metabolism.

The invention relates to the inhibition of hair growth.
Arachidonic acid is released from membrane lipids in response to injury or other irritation. The enzyme cyclooxygenase converts arachidonic acid into cyclic endoperoxides commonly known as PGG2 and PGH2. The endoperoxides subsequently are converted into prostoglandins, which are the primary mediators of inflammation in the body.
The enzyme 5-lipoxygenase converts arachidonic acid into 5-hydroperoxyercosa-6,8,11,14-tetraenoic acid, which subsequently is converted into a family of compounds known as leukotrienes. The exact biological role of leukotrienes has not yet been determined.
It has now been found that mammalian (including human) hair growth can be inhibited by applying to the skin a composition including an inhibitor of an enzyme involved in arachidonic acid metabolism in an amount effective to reduce hair growth in the applied area. The inhibitor may, for example, be an inhibitor of cyclooxygenase or lipoxygenase, or may inhibit both enzymes.
Some preferred inhibitors are commonly known as non-steroidal anti-inflammatory drugs (NSAIDs). These drugs include compounds from a variety of chemical classes.
One preferred class of NSAIDs are propionic acids, which include xcex1-methyl-4-[2-methylpropyl]benzeneacetic acid (ibuprofen), 6-methoxy-xcex1-methyl-2-naphthaleneacetic acid (naproxen), 2-[3-phenoxyphenyl]propionic acid (fenoprofen), 2-[3-benzoylphenyl]propionic acid (ketoprofen), gamma-oxo-[1,1xe2x80x2-biphenyl]-4-butanoic acid (fenoprofen), and 6-chloro-xcex1-methylcarbazole-2-acetic acid (carprofen).
Another preferred class of NSAIDs are indoleacetic acids, which include 1-[p-chlorobenzoyl]-5-methoxy-2-methylindole-3-acetic acid (indomethacin), 5-fluoro-2-methyl-1-[(4-(methylsulfinyl)phenyl) methylene]-1H-indene-3-acetic acid (sulindac), 1-methyl-5-[p-toluoyl]pyrrole-2-acetic acid (tolmetin), 2-[(2,6-dichlorophenyl)amino]-benzeneacetic acid (diclofenac).
A third preferred class of NSAIDs are salicylates, which include 2-acetoxybenzoic acid (acetylsalicylic acid) and 5-[2,4-difluorophenyl]salicylic acid (diflunisal).
A fourth preferred class of NSAIDs are anthranilic acids, which include 2-[(2,6-dichloro-3-methylphenyl) amino]benzoic acid (meclofenamic acid) and 2-[(2,3-dimethylphenyl) amino]benzoic acid (mefenamic acid).
A fifth preferred class of NSAIDs are enolic acids, such as 4-hydroxy-2-methyl-N-2-pyridinyl-2H-thieno[2,3-e]-1,2-thiazine-3-carboxamide-1,1-dioxide (tenoxicam).
Other NSAIDs like 4-[6-methoxy-2-naphthyl]-2-butanone (nabumetone) also can be used.
Examples of other inhibitors that have been found effective in reducing hair growth include quercetin (3,3xe2x80x2,4xe2x80x2,5,7-pentahydroxy flavone), dl-xcex1-tocopherol, apigenin (4xe2x80x2,5,7-trihydroxy flavone), propyl gallate, NDGA (nordihydroguaiaretic acid), and caffeic acid (3,4-dihydroxycinnamic acid). All of these compounds are known in the art and are commercially available. Other inhibitors are known in the art; see, for example, Laughton et al., 42 Biochemical Pharmacology 1673 (1991).
The composition preferably includes a non-toxic dermatologically, acceptable vehicle or carrier which is adapted to be spread on the skin. Examples of suitable vehicles are acetone, alcohols, or a cream, lotion, or gel which can effectively deliver the active compound. In addition, a penetration enhancer may be added to the vehicle to further enhance the effectiveness of the formulation.
The concentration of the inhibitor in the composition may be varied over a wide range up to a saturated solution, preferably from 1 to 30% by weight or even more; the reduction of hair growth increases as the amount of inhibitor applied increases per unit area of skin. The maximum amount effectively applied is limited only by the rate at which the inhibitor penetrates the skin. Generally, the effective amounts range from 100 to 3000 micrograms or more per square centimeter of skin.
The composition should be applied to the area of the body where it is desired to inhibit hair growth. Typically, the composition can be applied to the face, particularly to the beard area of the face, i.e., the cheek, neck, upper lip, and chin. The composition can also be applied to the legs, arms, torso or armpit. The composition is particularly suitable for the treatment of hirsutism. In humans, the composition should be applied once or twice a day, or even more frequently, for at least three months to achieve a perceived reduction in hair growth.
Reduction of hair growth is demonstrated when the frequency of hair removal is reduced, or the subject perceives less hair on the treated site, or quantitatively, when the weight of hair removed by shaving (i.e., hair mass) is reduced. Male intact Golden Syrian hamsters are considered acceptable models for human beard hair growth in that they display oval shaped flank organs, one on each side, each about 8 mm. in major diameter, which grow thick black and coarse hair similar to human beard hair. These organs produce hair in response to androgens in the hamster.
To evaluate the effectiveness of a particular inhibitor in reducing hair growth, the flank organs of each of a group of hamsters are depilated by applying a thioglycolate based chemical depilatory (Surgex). To one organ of each animal 10 xcexcl. of vehicle alone once a day is applied, while to the other organ of each animal an equal amount of vehicle containing the inhibitor is applied. After thirteen applications (one application per day for five days a week), the flank organs are shaved and the amount of recovered hair (hair mass) from each is weighed. Percent-reduction of hair growth is calculated by subtracting the hair mass (mg) value of the test compound treated side from the hair mass value of the vehicle treated side; the delta value obtained is then divided by the hair mass value of the vehicle treated side, and the resultant number is multiplied by 100.