CS270790B1 - Universal base for suspensions or emulsions - Google Patents

Abstract

The solution relates to a universal base for suspensions or emulsions, which, in addition to common pharmaceutical, cosmetic and food vehicles, contains xanthan polysaccharide and sodium dioctyl sulfosuccinate. 3e widely applicable for suspensions or emulsions used internally and externally. 3e applicable in pharmacy, cosmetics, food, veterinary medicine and a number of technical fields.

Description

The invention relates to a universal base composition for suspensions and emulsions with advantageous physiological properties, to a surfactant and to a pharmaceutical excipient which modifies the flow properties of the resulting suspension or emulsion. emulsion.

A large number of substances modifying the flow properties of suspensions, resp. emulsions, and surfactants enabling the processing of active, resp. pharmaceutical excipients for suspension, reap, emulsion.

Such properties of suspensions can be influenced by many pharmaceutical excipients, which belong to the hydrocolloids both of plant origin and to the group of semisynthetic substances. Inorganic substances with similar properties cannot be neglected.

Many active substances are difficult to process into suspensions without the aid of surfactants, resp. they are unprocessable. For this reason, a large number of cationic, anionic and nonionic surfactants are used. In materia pharmaceutica cationic substances, the choice is the narrowest and also the large number of incompatibilities is another obstacle to their use. Cationic surfactants are not suitable for oral use. The easiest way to find a suitable excipient is among countless non-iontogenic surfactants, but for which the physiological action is often decisive for their selection. The interaction between non-ionic surfactants and a number of preservatives is also not negligible, where the effect of preservatives is weakened or even lost. Anionic substances are quite narrow in terms of assortment and their physiological tolerability, especially non-irritancy, also plays an important role in many, and there are also a large number of incompatibilities in this group of substances. After summarizing the above facts, it can be stated that it is necessary to find a pharmaceutical excipient, which belongs to any group according to ionogenicity, must be physiologically well tolerated, sufficiently reduce surface tension and be fully compatible with all components. emulsion. The greatest emphasis is placed on the complete elimination of the interaction with the pharmaceutical excipient modifying the flow properties of the suspensions, in the sense of the formation of incompatibility. When monitoring individual excipients from the group of surfactants, their advantage in terms of technological processing and the development of incompatibilities were monitored, but above all physiological parameters such as skin irritation, gastrointestinal irritation, origin and occurrence of other side effects were considered.

In the search for excipients from the group of substances modifying flow properties, the procedure was similar and the main emphasis was also placed on physiological properties in addition to other advantageous parameters, such as ease of technological processing and the possibility of incompatibility. Unexpectedly, it has been found that the described shortcomings and problems are eliminated by the universal basis for suspensions, resp. emulsion, according to the invention, which consists of a combination of two pharmaceutical substances used exactly.

Their precisely defined properties were used, which are further explained in detail. Extensive practical testing confirmed the theoretical assumptions used for the testing.

The basis for the suspension, resp. The emulsion contains a combination of xanthan polysaccharide in an amount of 0.1% by weight to 1% by weight, sodium dioctylsulfosuccinate in an amount of 0.05% by weight, up to 1% by weight, chemical, microbiological and water stability agents. Other pharmaceutical excipients are used primarily in relation to the active ingredients, which are essentially suspended or emulsified.

Furthermore, the subject matter of the invention is illustrated by way of examples, without being limited thereto.

CS 270790 B1 example 1

Dermal suspension

Zinc oxide 15.00 % mass Xanthan polysaccharide 0.30 % mass Sodium dioctylsulfosuccinate 0.25 % mass Dowicil ^K 200 0.20 % mass Purified water up to 100.00 % mass

η

Note: Dowicil is a trademark of Dow, U.S.A.

- for chemical preservative:

cis isomer 1- (3-chloroalkyl) -3,5,7 triaza

1-azoniaadamantane hydrochloride

Water, xanthan polysaccharide, sodium dioctylsulfosuccinate are charged to the homogenizer at room temperature, and after complete homogenization, zinc oxide, Dowicil 200 and the rest of the water are added to this mixture. After homogenization again, the mixture is defoamed and filled.

Example 2

Antac idum

Precipitated calcium carbonate 20.00 % mass Xanthan polysaccharide 0.30 % mass Sodium salt of dioctylsulfosuccinate 0.25 % mass Calcium propionate 0.10 % mass Dowicil 200 0.20 % mass Water-soluble aroma-mandarin 0.15 % mass Water read to 100.00 % mass

Water at ambient temperature, xanthan polysaccharide, sodium dioctylsulfosuccinate are charged to the homogenizer and, after complete homogenization, calcium propionate, Dowicil 200, calcium carbonate are added to this mixture and the whole mixture is completely homogenized. The aroma of the remaining water is then added, and after re-homogenization, the mixture is defoamed and filled.

Example 3

Antac idum

Colloidal aluminum hydroxide (as 100%) 7.50 % mass Xanthan polysaccharide 0.30 % mass Sodium salt of dioctylsulfosuccinate 0.25 % mass parahydroxybenzoic acid propyl ester 0.15 % mass Aroma mint water soluble 0.10 % mass Water read to 100.00 % mass

Colloidal aluminum hydroxide is added to the homogenizer, xanthan polysaccharide, sodium dioctylsulfosuccinate are added and, after complete homogenization, parahydroxybenzoic acid propyl ester dissolved in aroma is added to this mixture, followed by the remainder of the water. Know at ambient temperatures.

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Example 4

Dermal suspension

Talc 20.00% by weight

Xanthan polysaccharide 0.30% by weight

Sodium salt of octylsulfosuccinate 0.25% by weight

A mixture of methyl and propyl parahydroxybenzoate (4: 1) 0.20% by weight.

Purified water up to 100.00 wt.

Water, xanthan polysaccharide, sodium octylsulfosuccinate are charged to the homogenizer at ambient temperature and everything is perfectly homogenized. Talc and preservatives dissolved in the rest of the water are added to this mixture. Homogenize again. The resulting suspension is defoamed and adjusted.

Example 5

Dermal suspension

Zinc sulphate heptahydrate

Calcium hydroxide

Xanthan polysaccharide

Sodium salt of octylsulfosuccinate Lactic acid 80% by weight.

Purified water

14.72 wt. 3.56% by weight 0.30% by weight 0.25% by weight 2.00% by weight to 100.00% by weight

At ambient temperature, water, zinc sulfate heptahydrate, calcium hydroxide, xanthan polysaccharide, sodium dioctylsulfosuccinate and lactic acid are charged to the homogenizer. After complete homogenization, sorbic acid dissolved in purified water is added and completely homogenized again. After foaming, it is adjusted.

Example 6

Hepatoprotective agent

Silymarin (mixture of plant bioflavonoids) 10.00 % mass Xanthan polysaccharide 0.30 % mass Sodium salt of dioctylsulfosuccinate 0.25 % mass Sodium cyclamate 3.00 % mass Sorbic acid 0.15 % mass Benzoic acid 0.15 % mass Citric acid 2.00 % mass Žluř SY 0.10 % mass Mixed water-soluble aroma of lemon and tangerine 0.20 % mass Water purified to 100.00 % mass

Example 6 - Method of preparation

At ambient temperature, xanthan polysaccharide, sodium dioctylsulfosuccinate, sodium cyclamate and a yellow dye are charged to freshly boiled water in a homogenizer. After complete homogenization, silymarin is added and a homogeneous mixture is again prepared, to which citric acid and benzoic acid and sorbic acid dissolved in aromatics are added. After homogenization, the rest of the water is added, followed by further homogenization, defoaming and filling.

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Example 7

Sunscreen

Olive oil. Xanthan polysaccharide 20.00% by weight 0.30% by weight Sodium salt of dioctylsulfosuccinate 0.25% by weight UF filter A 0.50% by weight 2-bromo-2-nitropropane 1,3-diol 0.05% by weight, Lactic acid 2.00% by weight Purified water up to 100.00% by weight,

Note; UF - filter A (for example: Parsol 1878, Givaudan)

Water, xanthan polysaccharide, sodium dioctylsulfosuccinate are charged to the homogenizer at ambient temperature, the whole is completely homogenized, then olive oil and UF - filter A, 2-bromo-2-nitropropane 1,3-diol, lactic acid and the residue are added. water, after re-homogenization it defoams and adjusts.

Example 8

Antacid

Magnesium oxide Xanthan polysaccharide 10.00 wt. 0.30% by weight Sodium salt of dioctylsulfosuccinate 0.25% by weight Saccharin soluble 0.12 wt. Sodium cyclamate 1.00% by weight Aroma mint water soluble 0.30% by weight Purified water. up to 100.00% by weight

At ambient temperature, xanthan polysaccharide, sodium dioctylsulfosuccinate, soluble saccharin, sodium cyclamate are charged to water in a homogenizer and the mixture is completely homogenized. then the aroma and the rest of the water are added. After homogenization, the defoaming fills.

Example 9

Antiulcerosum

Gallan bismuth 10.00 % mass Xanthan polysaccharide 0.30 % mass Sodium salt of dioctylsulfosuccinate 0.25 % mass Sodium benzoate 0.20 % mass Purified water up to 100.00 % mass

Example 9 - Method of preparation

Sodium dioctylsulfosuccinate and sodium benzoate are added to the xanthan polysaeharide in water at ambient temperature in a homogenizer. After homogenization, basic bismuth gallan and residual water are added. The homogeneous mixture is defoamed and adjusted.

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Example 10

Calcium and phosphorus donor

Calcium phosphate Xanthan polysaccharide Sodium salt of dioctylsulfosuccinate Phosphoric acid (85% by weight) Sorbic acid Water-soluble mango aroma Purified water

5.00 % mass 0.30 % mass 0.25 % mass 0.50 % mass 0.15 % mass 0.20 % mass to 100.00 % mass

Sodium dioctylsulfosuccinate, phosphoric acid are added to the xanthan polysaccharide in purified water in a homogenizer at ambient temperature, and the mixture is completely homogenized. Then sorbic acid dissolved in aroma and the rest of the water are added. After homogenization and defoaming, it fills.

Example 11

Antibiotic suspension

Chloramphenicol base 5.00% by weight

Xanthan polysaccharide 0.30% by weight

Sodium dioctylsulfosuccinate 0.25% by weight

Sodium sulphite 0.15% by weight

Ethylenediaminetetraacetic acid disodium salt 0.05% by weight.

Sodium benzoate 0.20% by weight

Purified water up to 100.00 wt.

Water, xanthan polysaccharide, sodium dioctylsulfosuccinate, disodium ethylenediaminetetraacetic acid, sodium sulfite and sodium benzoate are charged to the homogenizer. After complete homogenization, the rest of the water is added, mixed again, defoamed and adjusted.

Example 12

Antiulcerism, local anesthetic.

Oxethazain 10.00 wt.

Xanthan polysaccharide 0.30% by weight

Sodium dioctylsulfosuccinate 0.25% by weight

Sodium ascorbate 0.20% by weight

Sodium sulphite 0.15% by weight

Sodium benzoate 0.20% by weight

Purified water up to 100.00 wt.

The xanthan polysaccharide and sodium dioctylsulfosuccinate are homogenized in water in a suitable device at ambient temperature. Oxethazine, sodium sulfite, sodium ascorbate, sodium benzoate and the remainder of the water are added to the mixture. After rehomogenization, the mixture is defoamed and adjusted.

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Example 13

Laxative

Frangulaemodin docusat 10.00 % mass Xanthan polysaccharide 0.30 % mass Sodium salt of dioctylsulfosuccinate 0.25 % mass Sodium sulfite 0.15 % mass Sorbitol 20.00 % mass Caramel aroma (water soluble) 0.30 % mass Sodium benzoate 0.15 % mass Purified water up to 100.00 % mass

In a suitable homogenizer, a mixture of xanthan polysaccharide and sodium dioctylsulfosuccinate is prepared in purified water at ambient temperature. Then sorbitol, sodium sulfite, frangulaemodine docusate, sodium benzoate, aroma and the rest of the water are added. After further homogenization, it is defoamed and adjusted.

Example 14

Veterinary preparation - antitrematodic

(3>, (S'-bis-4-acetamidophenyloxyethyl ether 18.00 % mass Xanthan polysaccharide 0.30 % mass Sodium salt of dioctylsulfosuccinate 0.25 % mass Sodium sulfite 0.20 % mass Disodium salt of diaminotetraacetic acid 0.10 % mass Parahydroxybenzoic acid methyl ester 0.15 % mass Disodium phosphate dodecahydrate 0.60 % mass Citric acid monohydrate 0.05 % mass Purified water up to 100.00 % mass

Xanthan polysaccharide, sodium dioctylsulfosuccinate, methyl parahydroxybenzoate, disodium diaminotetraacetic acid, citric acid, disodium phosphate, sodium sulphite and the active substance are dispersed in boiled water in a homogenizer. After perfect homogenization, it defoames and fills.

The active substance acts against moths, especially their developmental stages. Pharmacological examination was performed at a dose of 1,500 mg, kg-1 when administered orally to sheep. The mean lethal dose of the substance in mice is higher than 3,000 mg.kg live weight. The tolerability of the suspension was also tested in lambs, histology, hematological and other biochemical parameters were monitored. The efficacy of the preparation ranged from 70 to 97%. The product was similarly evaluated helmintologically and was found to provide 100% efficacy against juvenile forms of moths and to reduce the intensity of invasions.

from a technological point of view, the product is easy to prepare and the stated composition is stable for 3 years under normal storage conditions.

Example 15

Veterinary preparation

3,5,6,3 ', 5'-pentachloro-2,2-dihydroxy-benzanilide 20.00 % mass Xanthan polysaccharide 0.30 % mass Sodium salt of dioctylsulfosuccinate 0.25 % mass Sodium sulfite 0.10 % mass Parahydroxybenzoic acid methyl ester 0.15 % mass Water purified to 100.00 % mass

CS 270790 Bl 7

In a ββ homogenizer, methyl parahydroxybenzoate and sodium dioctylsulfosuccinate are added to the xanthan polysaccharide to the xanthan polysaccharide, all homogenized perfectly. then the active ingredient and sodium sulfite are added, homogenized again. It expands after foaming.

Example 16

β, β-bis-4-acetamidophenyloxyethyl ether 9/00% mass Xanthan polysaccharide 0.30% mass Sodium salt of dioctylsulfosuccinate 0/25% mass Sodium saccharin 0.15% mass Mixed fruit aroma water soluble 0/20% mass Sodium sulfite 0/10% mass Parahydroxybenzoic acid methyl ester 0.10% mass ’ Citric acid 0.05% mass Purified water up to 100.00% mass

In a homogenizer, sodium dioctylsulfosuccinate is added to the xanthan polysaccharide in purified boiled water and the whole is completely homogenized. To the mixture

saccharin, sodium sulfite, acid are added lemon and v Aroma dissolved methyl ester parahydroxybenzoic acid and the whole amount active substance. After re-homogenization foaming and filling. Example 17 Cosmetic product Zinc stearate 10.00 % wt. Xanthan polysaccharide 0.10 % wt. Sodium salt of dioctylsulfosuccinate 1.00 % wt. Macrogol 4,000 lanolin (50%) 4.00 % wt. perfume water soluble composition 0.10 % wt. 2-bromo-2-nitropropane 1,3-diol 0.05 % wt. Lactic acid 0.80 % wt. Purified water up to 100.00 % wt In the homogenizer, it is cleaned water adds to xanthan polysaccharide

sodium salt of dioctylsulfosuccinate and perfectly homogenizes. Zinc stearate, macrogol 4,000 lanolin, perfume, 2-bromo-2-nitropropane 1,3-diol and lactic acid are added to the mixture. After homogenization again, the defoaming is adjusted and adjusted.

Example 18

Veterinary preparation

Methyl 5- (phenylthio) -2-benzimidazole carbamate 5.00 0 / / 0 mass Xanthan polysaccharide 0.50 % mass Sodium salt of dioctylsulfosuccinate 0.25 % mass Sodium citrate 0.10 % mass Citric acid 1.50 % mass Parahydroxybenzoic acid methyl ester 0.12 % mass Parahydroxybenzoic acid propyl ester 0.02 % mass Water purified to 100.00 % mass

CS 270790 Bl

In a homogenizer, sodium dioctylsulfosuccinate is added to the xanthan polysaccharide in purified water and thoroughly homogenized. sodium citrate, citric acid, both esters of parahydroxybenzoic acid are dissolved in the mixture. The mixture is made up to volume with water and completely homogenized. after foaming it fills up.

Example 19

Base for suspension prepared at the time of need

Xanthan polysaccharide 0.300 wt.

Aerosol OT - 70 0.325 wt.

Aerosil ^R - 200 ad 1,000 wt.

n

Aerosil - colloidal silica (Degussa)

Processing procedure

Aerosol OT-70 is mixed with xanthan polysaccharide and AeroO silo in a homogenizer. It is further processed on a granulate extruder.

Example 20

Base for emulsion prepared at the time of need

Xanthan polysaccharide 0.300 wt.

Aerosol OT - 70 0.325 wt.

Beet sugar ad 1,000% wt.

Aerosol OT - 70 - is a protected name for a 70% solution of dioctylsulfosuccinate in 1,2-propanediol

Processing procedure

In the homogenizer, Aerosol OT - 70 is mixed with xanthan polysaccharide and beet sugar. It is further processed on a granulate extruder.

Xanthan polysaccharide (xanthan gum, Xanthan Gummi). is given in National Formulary (nF XVI), Washington 1985.-Characterized in Food Chemicals codex, 2, nd.Ed. 1972, National Academy of Sciences, Washington, D.C. on page 856. It is essentially a natural polysaccharide with a high molecular weight of 2,000,000, but is also reported to be 13,000,000 to 50,000,000 (Dintzis, FF, Babcock, GE, and Tobin R., 1970. Carbohyd. Res. 13, 257 - 67). It is produced by fermentation of glucose in a suitable medium using the microorganism Xanthomonas campestris (Oeanes, A. R., Pittsley, 0. E., and Senti, F. R. 1961, 0. Appl. Polymer sci. 5, 519-526). The 3rd molecule consists of three monosaccharides - mannose, glucose and glucuronic acid (Sloneker, H., and 3eanes, A. R. 1962. Can. 3. Chem. 40, 2066-71).

It is characterized by:

Excellent chemical stability in solution, viscosity is independent of temperature up to 100 ° C, even in the presence of electrolytes, viscosity is independent of pH, it is possible to directly dissolve xanthan polysaccharide in 10% by weight, hydrochloric acid solution and also without damage of potassium hydroxide up to a concentration of 20% by weight, is soluble in hot and cold water, the solution is stable to the effects of frost, even at low concentrations of xanthan polysaccharide a high viscosity of the solution is achieved. Physiologically, it is completely indifferent even at high doses.

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Sodium dioctylsulfosuccinate

Synonyms; Sodium dioctylsulfosuccinate, Dioctyl sodium sulfosuccinate, Aerosol OT, Sulfimel DOS 100, Alphasol OT, Vatsol OT, Doxinate

Chemical nomenclature: Bis- (2-ethylhexyl) -nitrile sulfosuccinate

Summary formula: C _{2 O} H ₃₇ NaO ₇ S

Molecular Weight: 444.57

Classification: wetting agent (reduction of surface tension), solubilizer, emulsifier, plasticizer, also as a drug (laxative).

Biochemical aspects

Data on absorption and excretion mechanism are not available, but surfactants are known to be absorbed through the skin and possibly also through the mucosa.

Rat

³⁵ S-labeled sodium dioctyl sulfosuccinate was administered orally in a single dose in a mixture of alcohol and water (1: 1, V / V) to white rats weighing 200 g. The animals were fed and watered ad libitum. More than 85% of the administered sodium dioctylsulfosuccinate was excreted within 24 to 28 hours after administration and complete excretion occurred within 96 to 120 hours. 25 to 35% was excreted in the urine 24 to 48 hours after administration, after which time only trace amounts of this substance were excreted. The faeces contain more than 66% (radiolabeling) and the gastrointestinal tract has been shown to be the major route of excretion. Rat tissues 96 to 168 hours after dosing contain only traces of radiolabelled substance.

In another study, two rats were given a single oral dose of 5 mg or 10 mg of sodium dioctylsulfosuccinate in water and two rats were given a single intravenous dose of 10 mg. Five rats received a single oral dose of 5.8 mg 2-ethylhexanol in 40% ethanol. Of the total dose administered, 18.6% and 15.5% were excreted in the urine and 0.9 and 8.7% in the faeces within 24 hours, after oral administration of 5 or 10 mg. Animals that received dioctyl sulfosuccinate i.v. excreted 12.3 to 15.5% in the urine over 24 hours and not in the faeces. The urine sample obtained 24 to 48 hours from the test animals did not show a detectable trace of 2-ethylhexanol. Rats that received 2-ethylhexanol excreted 3.1% of the dose in the urine and 3.8% in the faeces within 24 hours after administration.

The male rat received 100 mg / kg body weight of ¹⁴ C-radiolabelled sodium dioctylsulfosuccinate. 64.1% of the radioactivity was excreted in the urine within 24 hours and approximately 1% within 24 to 48 hours. During the same time period, 27.4% resp. 0.9%. Dioctyl sulfosuccinate is extensively metabolised in rats because it is present in the urine and only a small amount is present in the faeces.

Rabbit i.

Two female rabbits received 4 mg of ¹⁴ C-labeled sodium dioctylsulfosuccinate, one animal orally and the other intravenously. Each route of administration resulted in more than 90% of the radioactivity excreted in the urine (87% and 69.7%, within 24 hours of administration, orally or iv). Analysis of a urine sample (24 hours) showed the same metabolites, independent of the route of administration.

CS 270790 Bl pes

Two dogs (beagles) were given radiolabeled sodium dioctylsulfosuccinate at 4 mg / kg body weight, one orally and the other intravenously. Analysis of the blood for 2-ethylhexanol showed that in the case of i.v. administration, the level of this substance in the blood decreases rapidly during the first hour and is zero at the eighth hour. After oral administration, there is a small amount of the substance in the blood after the first hour and the level is zero at eight o'clock. Each route of administration leads to similar conclusions on the mode of metabolism. About 21% of the radioactivity is excreted in the urine during the first 24 hours, the rest of the radioactivity is excreted in the faeces (70%) within 24 to 48 hours after administration.

Toxicological studies

Acute toxicity

Animal LD ₅₀ mg / kg

Rat 1,800 p.o.

Mice 3,980 p.o.

Mouse 1,500 p.o.

Mice tolerated 0.2 ml of 5% sc solution, although alcetation and necrosis developed at the injection site, or 0.5 ml of 0.2% sodium dioctylsulfosuccinate ip or 0.25 ml of 0.5% iv substance, which often led to hemolysis . Skin irritation tests with 1% sodium dioctylsulfosuccinate did not show irritation.

Short-term studies

Rat

A group of five male rats were fed 0%, 2%, 4% and 8% sodium dioctylsulfosuccinate for 16 weeks. It was recorded from slow growth at a concentration of 2% without death, one animal died at a concentration of 4% and all animals died within a week at a concentration of 8% from gastrointestinal disorders.

A small group of five male rats and five female rats were administered Oj 0.19) 0.37) 0.55) 0.75) and 0.87 g / kg body weight of sodium dioctylsulfosuccinate for 24 weeks, no deaths were observed, but weight reduction compared to control was observed. No significant effect on blood was observed. The histology of the liver, spleen, kidneys, pancreas, stomach, bladder, gonads, heart, lungs, brain and spinal cord showed nothing remarkable.

In another experimental group, 12 male and 12 female rats were administered 0 (0.5% (1/04%) and 1.4% sodium dioctylsulfosuccinate for 26 weeks. No significant difference was observed between test substance-fed and control animals, except in females, which showed a slight decrease at 1% and 1.5% after three weeks, with no adverse effects on blood, urine, food intake, and spleen weight. , liver, adrenal glands, kidneys, gonads, as well as in the histology of the heart, lungs, liver, spleen, kidneys, adrenal glands, urine. bladder, thyroid, pancreas, muscles, bones, gonads and thymus. Two animals from the control group and four from the tested group (1.5% of the amount) died, of which 2 for hejioragic gastroenteritis.

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Rabbit '

Seven rabbits were administered 0.5 g of sodium dioctylsulfosuccinate intragastrically per kg of body weight daily for 24 weeks. Three animals died of massive diarrhea and anorexia, two of unknown causes and two animals survived without pathological symptoms on macroscopic and histological examination of the liver, spleen, kidneys, pancreas, urine. bladder, gonads, heart, lungs, intestines and CNS.

On ice

Three monkeys received 0.125 g of sodium dioctylsulfosuccinate per kg of body weight daily for 24 weeks. Higher doses for gastrointestinal irritation were not tolerated. No pathological symptoms in macroscopic and histological examination of liver, spleen, pancreas, kidneys, intestines, urine. bladders, gonads, heart, lungs and CNS were not detected.

Dog

Groups of three dogs received 0.1 mg or 0.25 mg per kg body weight for 24 weeks. Higher doses showed gastrointestinal irritation. All dogs lost weight, but this was not attributed to sodium dioctylsulfosuccinate. Macroscopic and histopathological examination did not show any abnormalities in the liver, spleen, pancreas, kidneys, intestines, urine. bladder, gonads, heart, lungs and CNS.

Long-term studies

Rat

Groups of twelve male rats were given 0 * 0.25% * 0.5% ’and 1% sodium dioctylsulphosuccinate in the diet for two years. Body weight decreased slightly at 1% concentration during the first three months and was more pronounced during the first year. No pathological changes were observed on macroscopic examination and histological examination of the lungs, heart, liver, spleen, pancreas, stomach, intestine, kidneys, adrenal glands, gonads, thyroid, parathyroid glands, bones and muscles.

Observations in humans

Sodium dioctylsulfosuccinate is used as a laxative (emollient) in huge amounts and for many years (since 1943) in children and adults.

In chronic constipation, it is used as an emollient, but not laxative, the effect occurs one to two days after administration. The recommended dose is 10 to 20 mg per day for children, 10 to 60 mg for adults (daily), exceptionally 100 mg. from 300 mg we can expect side effects.

r

CS 270790 Bl

Summary

Amount that does not cause symptoms of intoxication:

Rat - 0.5% (5,000 ppm) in food, equivalent to 250 mg / kg body weight

Using material: Wld. Hlth. Org. Techn. Rep. Ser., No. 557 (1974) Toxicological Evaluation of some Food colors, Enzymes, Flavor Enhancers, Thickening Agents, and certain Food Additives / Dioctyl Sodium Sulfosuccinate pp. 175 - 181 /.

Claims (1)

OBJECT OF THE INVENTION Universal base for suspensions or emulsions used in pharmacy, cosmetics and food industry in the form of a solution or powder mixture, optionally with the addition of customary excipients, characterized in that it contains 0.05 to 1% by weight of sodium dioctylsulfosuccinate and 0.1 to 1% mass, xanthan polysaccharide.