Emulsion lotion with active vitamin d3 |
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IPC classes for russian patent Emulsion lotion with active vitamin d3 (RU 2207843):
               
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The invention can be used in pharmacology and cosmetology to obtain a pharmaceutical composition. The lotion contains (a) a therapeutically effective amount of active vitamin D3(b) component of the oil phase containing the solid oil component comprising white vaseline and the higher alcohol, and a liquid oil component comprising squalane, (C) component of the aqueous phase containing the ionic polysaccharide and (d) a nonionic surfactant; and (1) the contents of the specified ionic polysaccharide is from 0.3 to 1.0 part by weight of the drug, (2) the contents of the specified higher alcohol is 0.2 - 1.0 part by weight of the drug, and (3) specified HLB nonionic surfactant has the meaning equal to 10 or more. The lotion is suitable for use in areas with hair, demonstrating satisfactory pharmacological activity, stability of the primary drug component and physical stability. 6 C.p. f-crystals, 15 tab., 2 Il.
The present invention relates to the emulsion lotion on the basis of active vitamin D3and especially, to the emulsion lotion on the basis of the active vitamin is built surface-active agent, in which ionic polysaccharide is contained in a component of the aqueous phase in a certain amount, the higher alcohol is contained in a component of the oil phase in a certain amount and HLB (hydrophilic-lipophilic balance) of the specified nonionic surface-active agent has a certain value.
Because, for example, 1 ,25-dihydroxycholecalciferol or 1,24-dihydroxycholecalciferol is a substance having the ability to regulate the content of CA, which, as you know, is the physiological function of vitamin D3this substance is referred to as the active vitamin D3. Although the physiological action of active vitamin D3is different, that, apparently, is connected with the ability of active vitamin D3to induce differentiation and to inhibit the growth data were obtained, confirming the fact that the active vitamin D3possesses effective against psoriasis, which resistenti skin disease, and the mechanism of its action consists in normalizing the lack of differentiation and accelerated growth of epidermal cells, which is believed to be the cause of ategorias, are diseases of the epidermis the outer layer of the skin, in terms of bioavailability is more profitable to make a local application, not system introduction in the form of oral administration, injections, etc. in Addition, this type of application is also preferred from the point of view of possible prevent unwanted systemic side effects. Examples of dosage forms for local use can be such semi-solid preparations like ointments and creams; such liquid preparations, as lotions and liniments; adhesive tapes; poultices and powders. However, given the pathology of psoriasis, the preferred forms are semi-solid preparations and liquid preparations.
Well-known examples of semi-solid preparations include oil ointments containing as the main medicines 1,24-dihydroxyvitamin D3and white petrolatum as a base (Japanese pokexperto.net patent publication 3-68009), cream preparations containing oil phase component comprising such a viscosity regulator, as cetyl alcohol and such the lipophilic solubilizer as liquid paraffin, such surface-active agent as sorbitol monostearate (span 60), and this component of the aqueous phase, as propilenglikola medicines 1,24-dihydroxyvitamin D3and containing a component of the oil phase, including such solid oil component as white petrolatum, surface-active compound comprising sodium lauryl sulfate, etc., and the component of the aqueous phase comprising propylene glycol, etc., (Japanese pokexperto.net patent publication 3-68009). In addition, an example of known drug in the form of cream contains, as essential medicine 1,24-dihydroxyvitamin D3and solid oil component comprising white petrolatum, etc., that component of the oil phase containing a liquid oil component comprising squalane, etc., such surface-active substance, as polyoxyethylene gidrirovannoe castor oil 60, and such a component of the aqueous phase as propylene glycol (publication WO 95/6482).
However, given the pathology of skin diseases, the preferred drugs for local use are liquid cosmetic preparations. Because, according to rough estimates, 1/3 of patients suffering from psoriasis on the hairy area of the scalp are hair lotions are the preferred drugs because they don't stick to the places where the hair is easily the nano is a since, according to the measurement carried out on a rotational Brookfield viscometer, using spindle LV4, when the rotation speed of 60 rpm and a temperature of 25oC). In addition, it is desirable that the viscosity had no significant influence of such external influences such as temperature or vibration, and that it remains constant. Moreover, since the pathology of psoriasis includes anomaly in which there is a destruction of epidermal skin cells, and there are indications of weak resistance to irritating substances, it is preferable that the drugs used for the treatment of psoriasis, had a low level irritant effect.
As a rule, liquid cosmetics can be roughly classified into lotions type of solution and lotions type emulsion.
From lotions with active vitamin D3, lotions type solution with calcipotriol or derivative (20)R-22-oxa-vitamin D3disclosed in the publication WO 91/12807 and publications WO 92/01454. Because these lotions applied solvent such as ethanol, gives the lotion a low viscosity, such drugs are not only easy to drain when applied, preventing the delay of the drug on disease-prone area is it in it should also be borne in mind irritant effect of such organic solvents, such as ethanol, is used as a solvent or amplifier absorption.
An example of a lotion type emulsion is described, for example, in Japanese patent laying 60-174705, and this lotion contains active vitamin D3and its derivatives, such component of the oil phase, as spermaceti wax, cetanol vaseline or squalane, such surface-active substance, such as monostearate polyoxyethylene (10 mol) or monooleate sorbitol, and this component of the aqueous phase as glycerin. In addition, in Japanese pokexperto patent publication 3-68009 also revealed the lotion emulsion type, which contains 1,24-dihydroxyvitamin D3component oil phase comprising such a solid oil component as stearyl alcohol and such a liquid oil component, as liquid paraffin, and a surfactant comprising sodium lauryl sulfate.
If these lotions type emulsion is stored, for example, at a temperature of 50oC or lower, or affect them vibration, there is a change in viscosity and observed the formation of gel.
Thus, it is possible to conclude that, stetsa pharmacological activity and chemical resistance of the main medicines the optimum viscosity, concerning, for example, help prevent sticking to the sections of hair, ensure ease of application and prevent runoff, issue sensations when applied, and physical stability of the drug in conditions of long-term storage, exposure to heat or vibration, etc.
The purpose of the present invention is to provide emulsion lotion with active vitamin D3that keeps the pharmacological activity and chemical stability of the basic drug in the form of active vitamin D3.
Another objective of the present invention is to develop emulsion lotion with active vitamin D3that retains pharmacological activity and chemical stability of the basic drug in the form of active vitamin D3and/or has excellent pharmacological activity and chemical resistance and has a viscosity suitable for application, for example, sections of the hair.
Another objective of the present invention is to provide emulsion lotion with active vitamin D3that retains pharmacological activity and chemical resistance of the primary drug srezkoy resistance, has a viscosity suitable for use, for example, on the sections of hair, has excellent physical stability during prolonged storage of the drug, or the influence of the heat and vibration, and is characterized by a low level irritant effect on the skin.
Taking into account the above objectives, the preliminary research on the development of emulsion lotion type oil-in-water (O/W) on the basis of active vitamin3satisfying the conditions (1) no adhesion, ease of application and with a viscosity that prevents spreading even when applied on the sections of hair, (2) preservation of pharmacological activity and chemical stability of the active vitamin D3sufficient for use as a pharmaceutical preparation, (3) provide sufficient physical stability for use as a pharmaceutical product, and (4) provide low level irritant effect on the skin, it has been found that the above objectives can be achieved by combining the use of special component of the oil phase, adding an ionic polysaccharide component to the aqueous phase, application of non-ionic surfactants, and tochnogo number specified ionic surfactants, a certain amount of the higher alcohol in the oil phase component and a HLB value for the specified nonionic surfactant that has led to the creation of the present invention.
More specifically, the present invention provides an emulsion lotion with active vitamin D3designed, for example, for the treatment of skin diseases, comprising: (a) a therapeutically effective amount of active vitamin D3(b) component of the oil phase containing the solid oil component comprising white vaseline and the higher alcohol, and a liquid oil component comprising squalane, (c) the aqueous phase containing an ionic polysaccharide, and (d) nonionic surface-active compound; where (1) the contents of the specified ionic polysaccharide is from 0.3 to 1.0 weight parts of the total weight of the preparation, (2) the contents of the specified higher alcohol is from 0.2 to 1.0 weight parts of the total weight of the preparation, and (3) HLB specified nonionic surface-active compound has a value of 10 or more.
In Fig.1 depicts a diagram showing an example of a method of production of lotions of the present invention.
Fig. 2 represents g is his invention and lotions comparative examples 9 and 10.
Component oil phase, which forms a lotion with active vitamin D3the present invention comprises a solid oil component comprising white vaseline and the higher alcohol and a liquid oil component comprising squalane.
White petrolatum present invention was purified by decolorization of mixture of hydrocarbons, obtained from petroleum, and the quality standards specified, for example, in the Japanese Pharmacopoeia, used as standards of quality. In particular, white petrolatum high purity are preferred for providing stability of the active vitamin3for example, 1,24-dihydroxyvitamin D3moreover , it is preferable to apply the vaseline peroxide number of the order of 0.5 or less.
In addition, squalane of the present invention is a saturated hydrocarbon, obtained, for example, the recovery of hydrocarbons produced from the oil of the liver oceanic sharks that live at great depths, and quality standards are stipulated, for example, in the Japanese standards of cosmetic raw materials are used as the quality standards of such hydrocarbons.
As was established using a test for primary skin irritation in rabbits, description is than these components polar oil phase, as esters of fatty acids. The use of such a component oil phase with a low level irritants allows you to get the lotion low irritant, which can be applied on the affected areas of skin, for example, in psoriasis.
In accordance with the present invention, it is preferable that the content of the higher alcohol ranged from 0.2 to 1.0 weight parts of total weight of the preparation. If this number is above 1.0 in weight. part, tend to impede the process of obtaining lotion with such a viscosity that will not change under the influence of heat or vibration. If this amount is less than 0.2 weight. parts, it is difficult for the formation of the protective layer (phase D) around the oil phase. As a result, increases the susceptibility of the system to the phenomenon of phase separation in the oil and water phases, which ultimately can lead to a significant reduction in chemical resistance the active vitamin D3.
A preferred example, the viscosity of the lotion of the present invention can serve as the viscosity of the lotion from 500 to 1400 MPaC, measured in a rotary viscometer Brookfield, using sleeve LV4, when the rotation speed of 60 rpm and those who omponent oil phase of the present invention, preferably form a solid oil component comprising from 2 to 5 parts by weight of white petrolatum and from 0.2 to 0.5 parts by weight of a higher alcohol, and a liquid oil component containing from 1 to 2.5 weight parts of squalane, in the quantity of intervals satisfying the above weight ratio between the solid oil component and a liquid oil component.
In addition to the above-mentioned white vaseline, higher alcohol and squalane, a component of the oil phase of the present invention may be added other solid oil and liquid oil components. Examples of the solid oil component can serve as solid paraffin, spermaceti wax and beeswax. These substances should be added in amounts lying in the intervals that achieve one of the purposes of the invention, for example, maintaining physical stability. As an example, add the number that can result in a 1/4 weight parts or less of the solid oil component of the present invention, which is preferred in terms of providing the viscosity of the lotion, suitable for application to those areas where there is hair. Examples of the liquid oil component can be such words is DCI paraffin and dimethylpolysiloxane. The added amount of such a liquid oil components must lie in the interval, which ensures the achievement of the purposes of the invention, for example, physical stability. For example, the quantity of squalane of the present invention, is equal to 1/2 the weight parts or less, is preferred to achieve the viscosity of the lotion, suitable for use in those areas where there is hair. Moreover, in regard to the irritating, it was found that the application of the oil phase component different from the component of the oil phase on the basis of hydrocarbons results in a slight increase irritation in comparison with the usage of a component of the oil phase on the basis of hydrocarbons.
To a component of the oil phase of the present invention may be added an antioxidant. Examples of antioxidants can serve as equivalent, butylhydroxyanisole and d1-tocopherol, preferably add d1-tocopherol. Usually, the specified number of antioxidant is from 0.001 to 2.0 weight parts, and more preferably, from 0.01 to 1.0 weight parts.
Component of the aqueous phase of the present invention with the statutory invention refers to a polysaccharide, a sugar chain containing, for example, carboxyl group or sulfate group and has the structure of a sugar chain, which ionizes in aqueous solution. Due to the presence of ionic polysaccharide, emulsion, lotion of the present invention is almost not affected by changes in viscosity when exposed to such external stimuli as heat or vibration. In addition, this component provides a means of stabilizing the emulsion, thus preventing the separation of the phases. Moreover, even when the active vitamin D3the main drug of the present invention, unstable in water, as is the case when 1,24-dihydroxyvitamin D3, an effect of preventing deterioration of stability of the basic medicines.
Examples of ionic polysaccharide can serve as xanthan gum and/or ceragenin, and xanthan gum is the preferred agent. The number of such ionic polysaccharides, preferably ranges from 0.3 to 1.0 weight parts of the total weight of the preparation, and more preferably, from 0.4 to 0.8 weight parts.
In addition, to the component of the aqueous phase may be added agent, uditi propylene glycol, glycerin and sorbitol, enter the amount from 1 to 20 weight parts, and preferably 2 to 15 weight parts. Examples of antiseptic agents can serve as parabens such as methyl paraben, propyl paraben and mixtures thereof, chlorbutanol, monothioglycerol, sorbic acid, potassium sorbate and benzyl alcohol added in quantities of from 0.001 to 10.0 weight parts, and preferably from 0.01 to 5.0 weight parts. Examples of chelating agents can serve as citric acid, sodium citrate and edetate sodium, added in quantities of from 0.001 to 5.0 weight parts, and preferably from 0.01 to 3.0 weight parts. As buffers can be used secondary acidic sodium phosphate, monopotassium phosphate and monopotassium phosphate potassium added in a weight ratio required to establish the pH component of the aqueous phase in the range of 6.5 to 8.5.
In the lotion of the present invention the weight ratio between the above-mentioned component of the oil phase component and the aqueous phase (oil phase component/component aqueous phase) is estimated in the range of 15/85-3/97. In the case of withdrawal within the specified interval, it is not possible to provide the above-mentioned viscosity and stability, preferred for application to contain nonionic surface-active compound. Such nonionic surface-active agent consists of two or more types of surfactants. Examples of such surface-active additives of the present invention include one or more types of surface-active compounds selected from the group consisting of such surfactants with low HLB, as monooleate sorbitol, sorbitol monostearate, sesquioleate sorbitol, trioleate sorbitol, glycerol monostearate, monooleate glycerin and monostearate propylene glycol, and such surfactants with a high HLB value, as orbitotemporal of polyoxyethylene (30, 40, or 60), castor oil, utverjdenie using polyoxyethylene hydrogenated castor oil 60, monolaurate sorbitol, monopalmitate sorbitol, monolaurate polyoxyethylene (20) sorbitol, monopalmitate polyoxyethylene (20) sorbitan, monostearate polyoxyethylene (20) sorbitol, monooleate polyoxyethylene (20) sorbitol, monolaurin of polyoxyethylene (10) cetyl ether of polyoxyethylene (23, 25, or 30). Usually, a surfactant with a low HLB value combined with surface-active substance with a high HLB value to control HLB to stabilize the emulsion.
The content of the nonionic surface weight of the preparation. In addition, in this case, it is preferable that the entire nonionic surface-active agent had an HLB value of 10 or more, and preferably of 11.0 or more, so that the above-mentioned ionic polysaccharide was able to show a preventive effect against phase separation. More preferably, the total content of nonionic surface-active compounds ranged from 11.5 to 14.5.
Examples of active vitamin D3the present invention can serve as an active vitamin D3selected from the group consisting of 1,24-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D3and 1-hydroxyvitamin D3. Preferred substances are 1,24(R)-dihydroxyvitamin D3and 1,24(S)-dihydroxyvitamin D3especially preferred agent because of its excellent pharmacological activity, is 1,24(R)-dihydroxyvitamin D3. In addition, crystalline form 1,24(R)-dihydroxyvitamin D3preferred in respect of purity and can be used, for example, 1 hydrat playmouse effective for the treatment of diseases of the skin, to which is applied the medicine and, usually, the concentration of this substance in the lotion has a value in the interval 0,00005 of 0.01 weight parts.
The lotion of the present invention with an active vitamin D3produced in accordance with conventional ways, by dissolving the desired amount of active vitamin D3component oil phase in the presence of surface-active compounds, when heated; mixing the resulting solution with a component of the aqueous phase or component of the aqueous phase, not containing solution of an ionic polysaccharide, which is heated in the emulsifying device; emulsifying the mixture with the formation of a homogeneous emulsion, or as needed, adding to the mixture solution of an ionic polysaccharide, followed by emulsification of the mixture with the formation of a homogeneous emulsion; and final cooling.
Lotion with active vitamin D3the present invention can be used as a therapeutic agent for the treatment of such skin diseases as psoriasis, pustular psoriasis, guttate psoriasis, eritrocitarnyi psoriasis, inverse psoriasis, severe psoriasis and other types of psoriasis and keratosis. Although the dosage may vary over with a concentration of 1,24-dihydroxyvitamin D3from 100 to 0.1 µg/g lotion, from one to several times a day.
Thus, it is proposed emulsion solution containing active vitamin D3with a viscosity that is suitable for application to areas where there is hair, with satisfactory pharmacological activity, stability, basic medicines and physical stability, and low irritation to the skin. In addition, it should be noted extremely high value development of such emulsion lotion with active vitamin D3for clinical practice.
Examples Although see below for further explanation of the present invention using examples of its embodiment, it should be noted that the invention is in no way limited to these examples. First, there is an explanation on the different types of testing methods used in the examples.
Brief description and purpose of test.
Table 1 outlines the purpose and content of tests are done.
Below is a detailed description of the test methods specified in table 1.
Test method 1: Method of test solution viscosity of the Sample lesionarse 12 mm and a depth of 50 mm, the filling was carried out before the glass threads to prevent the ingress of air bubbles. Testing was carried out in an environment at 25oWith the following conditions that meet the requirements set out in the section "Method for measuring the viscosity of the General methods of test of the Japanese Pharmacopoeia.
Method 2: method using a rotational viscometer.
Test conditions:Equipment: single-Cylinder rotational viscometer DV-II+ (Brookfield). Rotor: LV4 rotor. Rotation speed: 60 rpm Measurement: the viscosity was measured after the rotation of the rotor within 3 minutes. The basis of evaluation criteria served as the viscosity 500-1400 MPa with that adopted for the optimum viscosity (see Reference test 1).
Reference test 1: evaluation of the viscosity of the lotion using sensory testsThe ability to adhesion and ease of application was evaluated on the touch, and the spreading resistance was evaluated visually by comparison of commercially available lotions with subjects lotions. It should be noted that commercially available lotions were placed, and they were used from containers in which they were sold, while the subjects lotions were placed in polyethylene containerline examples A-D are described in table. 4. In accordance with the results shown in table 2, it was found that the optimum viscosity for effective achievement of the affected area, the safety of use and ease of handling when the external treatment of skin diseases when applied on the sections of hair, etc. is a value in the range of 500-1400 MPa.with. Test method 2: test Methods physical stability lotion 2-1. The test using the gravitational load Sample lotion weighing 1 g was placed in a centrifuge tube and was removed after centrifugation for 1 hour with a speed of 3750 rpm Investigated the appearance of lotion and have been checking for signs of separation of the oil and water phases. The evaluation criterion was the absence of signs of phase separation and stains. 2-2. The test using the heat load tests (heat) Eight grams of the sample of the lotion was placed in a glass tube for sampling. The tube was closed and then kept in a bath with a constant temperature of 50 or 40oC. Study the appearance of a lotion and the viscosity measurement was performed in time and the lotion was tested for the presence of signs of separation between water and oil phases, and change: Lotion with 1 ,24-dihydroxyvitamin D3Test method for chemical resistance 500 mg lotion was placed in a centrifuge tube, followed by adding 50 ál of internal standard (prednisolone, 100 μg/ml) and 5 ml of dichloromethane, after which the sample was centrifuged for 10 minutes at a speed of 3000 Rev/min and then was cooled to 5oAfter shaking for 10 minutes. The lower dichloromethane layer was removed and the part is subjected GHUR analysis to determine the number 1 ,24-dihydroxyvitamin D3. Used the following criteria GHUR:Column: Intertsil SIL 4.6 ñ 250 mm The column temperature: 40oC. Eluent: n-hexane/EtOH (89/11). Flow rate: 1 ml/min. Detector: UV 265 nm. Although according to the evaluation criterion of the residual norm of the main medicinal component in 95% or more accounts for its durability, taking into account the measurement error (  2%), the residual norm of the order of 93% or more is estimated, as preferred.
Test method 4: Lotion with 1,24-dihydroxyvitamin D3Test method pharmacological activity Cell-growth inhibitory activity of 1 ,24-digicable) activity as a marker of cell-growth activity. The growth of epidermal cells is accelerated in the treatment of skin devoid of hair mouse TPA (12-O-tetradecanoylphorbol-13-acetate), followed by the application of lotion with 1,24-dihydroxyvitamin D3and by measuring the inhibition of cell growth by ODS activity. In more detail, 10 nmol TRA initially applied devoid of a hairline site mouse back size 33 cm2in order to accelerate the growth of epidermal cells. Then, 50 mg of the test sample (lotion) was applied on the same area of the skin of animals of the group treated with the drug (animals of the control group, the lotion is not applied). Five hours later the skin at the site of application were cut and measured ODS activity in accordance with the method described Ciba, K., et al. (Cancer Res. , 44: 1387-1391 (1984)). The relationship between ODS activity group receiving the drug, and the corresponding value in the control group was used to represent the speed of inhibition, which, in turn, was used as an indicator of pharmacological activity lotion,24-dihydroxyvitamin D3.
The evaluation criterion was the equivalence of the action ointments Teijin Bonalpha Ointment is alas clinically. In addition, the equivalence of this kind is described in the test biological equivalence in accordance with the management of Pharmaceutical manufacturing guidelines (Yakugyo Jihosha Publishing).
Test method 5: Comparative testing method cumulative irritant to the skin of rabbits.
0.05 g of the product of example and comparative example was applied daily for 7 days (obtenida applique at the area of the dorsal skin (6,25 cm2) male Japanese white rabbits, with subsequent assessment of cumulative irritation (redness) of the back, in accordance with the valuation method for Dray.
Criteria of this assessment are presented in table 5. It should be noted that drugs with a rating below 1 in the results obtained on the 7th day, was assessed as having a low level irritant effect.
Example 1The composition prepared in Example 1 described in table 6, while the diagram of a method of obtaining shown in Fig.1. Explanation of method of cooking The above solid oil component (s 4-6), a liquid oil component (component 7) and nonionic surfactant (components 8-10) were mixed with each other and heated to 75-85oWith education odnorodnogo 2) in a solvent (component 3) was added to the above mixture followed by heating until a homogeneous dissolution (solution A). In addition, antiseptic (components 11 and 12), stabilizer (component 13), water-holding agent (component 14) and buffer (components 16 and 17) was heated to 75-85oWith in purified water (component 18) with the homogeneous solution (solution B). Ionic polysaccharide (as ionic polysaccharide used xanthan resin (component 15)) was dissolved in purified water to obtain a solution of an ionic polysaccharide (solution C). Solutions a, b and C were mixed in a vacuum emulsifier (Mizuho) for the purpose of emulsification and homogeneous primary emulsion. Then it was cooled to room temperature to obtain white lotion (Example 1). In addition, the numbers indicated for each component in table 2, can be used in the following examples and comparative examples, instead of the names of each of them in the example 1. Examples and comparative examples described in the text, prepared in accordance with the above method of obtaining a (Fig.1) on the basis of Example 1. Examples 2-10 and comparative examples 1-10 A summary of the examples and comparative examples are shown in table 7, and the compositions disclosed in tables 8-10. Tests on physical and chemical stability Physical stabilisations stability was determined according to test method 3. Evaluation criteria are presented in table 11 and the results are shown in table 12. In accordance with the data of table 12, lotions of examples 1-10 and comparative examples 9 and 10 were evaluated, as applicable, in accordance with the tests of gravitational and thermal load, held for investigation of the physical stability. Based on these data, it was found that physically stable lotion the resulting synergistic effects of three factors such as the weight amount of the higher alcohol, the weight amount of xanthan resin and the HLB value of a surfactant. In addition, it was found that the liquid cosmetic compositions, in which there is a separation of phases show very poor chemical resistance 1 ,24-dihydroxyvitamin D3and unable to maintain stability in case of their use as pharmaceuticals.
Moreover, lotions comparative examples 9 and 10 proved unsatisfactory in the following test irritant effect on the skin.
Test the pharmacological activity of the lotion of example 1The results of the tests on the pharmacological activity of lotion from prima and ointments Bonalpha from Teijin (ointment active 1 ,24-dihydroxyvitamin D3contained in the ointment in the amount of 2 µg/g), conducted in accordance with test method 4, presented in table 13.
According to the results of table 13, the lotion of the present invention (example 1) exhibits pharmacological activity 1,24-dihydroxyvitamin D3in animal models of psoriasis, equal activity ointment.
Test irritant effect of the lotion of example 1 on the skinThe results of comparative tests of cumulative irritant effect on the skin of rabbits lotion of example 1 (although it contains 2 µg/g 1 ,24-dihydroxyvitamin D3and the lotion of comparative example 9 (containing,24-dihydroxyvitamin D3at 2 µg/g), conducted in accordance with test method 5, shown in Fig.2.
Example 11.
The composition obtained as Example 11 shown in table 14, the method of obtaining such a composition in the General form shown in Fig.1.
Explanation of method of obtainingThe above solid component (s 4-6), a liquid oil component (component 7) and nonionic surfactants (components 8-10) were mixed and heated to 75-85oWith education antioxidant (component 2) in a solvent (component 3) was added to the mixture followed by heating until a homogeneous dissolution (Solution A). On the other hand, antiseptic (components 11-12), stabilizer (component 13), agent moisture retention (component 14) and a buffer agent (components 16 and 17) was heated to 75-85oWith in distilled water (component 18) with the homogeneous solution (Solution B). Ionic polysaccharide (xanthan resin was used as the ionic polysaccharide (component 15)) was dissolved in distilled water to obtain a solution of an ionic polysaccharide (Solution C). Solutions a, b and C were mixed in a vacuum apparatus for emulsification (Mizuho) for emulsification and homogeneous primary emulsion. Then it was cooled to room temperature to obtain white lotion (Example 11). Example 12 The composition obtained as Example 12, are presented in table 15, the method of obtaining such a composition in the General form shown in Fig.1. Explanation of method of obtaining The above solid component (s 4-6), a liquid oil component (component 7) and nonionic surfactants (components 8-10) were mixed and heated to 75-85oWith the formation of a homogeneous melt. Solution 1 -dihydroxyvitamin D3(component 1) and antioxidant (component 2) in a solvent (component 3) was added to the floor of komponenty 11-12), the stabilizer (component 13), agent moisture retention (component 14) and a buffer agent (components 16 and 17) was heated to 75-85oWith in distilled water (component 18) with the homogeneous solution (Solution B). Ionic polysaccharide (xanthan resin was used as the ionic polysaccharide (component 15)) was dissolved in distilled water to obtain a solution of an ionic polysaccharide (Solution C).
Solutions a, b and C were mixed in a vacuum apparatus for emulsification (Mizuho) for emulsification and homogeneous primary emulsion. Then it was cooled to room temperature to obtain white lotion (Example 12).
, 24-dihydroxyvitamin D3, 1, 25-dihydroxyvitamin D3and 1-hydroxyvitamin D3.
5. The lotion according to any one of paragraphs.1-4, wherein said ionic polysaccharide is a xanthan resin and/or carrageenin.
6. The lotion according to any one of paragraphs.1-5, the viscosity of which, measured at 25oWith, on a rotational Brookfield viscometer, using spindle LV4, rotating at 60 rpm, is from 500 to 1400 MPaC.
7. The lotion according to any one of paragraphs.1-6, where these skin diseases are psoriasis or keratosis.
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