HU212109B - Process for producing water in oil type microemulsive ointment containing pine-resin and beeswax - Google Patents

Abstract

Water in oil microemulsion based ointment of 600-4600 mPa viscosity contains (all wt.%): 17.5-22.5 pine resin, 17.5-22.5 beeswax. the total concn. of these components is 33-45 and the ratio of resin; wax=1.3:1-1:3. The ointment contains 35-55 liposomatic phase contg. 2.4-3.1 lecithin and 0:5-0.7 cholesterol; a 37.5-47.5 continuous liq. phase contains 0.2-0.7 natural prod(s) and 4.5-5.5 organic cosolvent phase. This cosolvent phase contains 0.5-1.5 di:methyl-iso-sorbitol cosiolvent, 2-4 natural cpds. 1-3 poly-ethylene-glycol-(9)-mono-dodecyl:ether and 4-15 of au aq. phase. The aq. phase contains 2-3 glyceol 0.2-1 magnesium-sulphate, 2-11 water and other additives to 100 wt%.

Description

The present invention relates to a process for preparing a water-in-oil microemulsion ointment having a viscosity of 6004600 mPas, preferably 600-3000 mPas.

It is known that many natural substances are used in folk medicine in gel and paste form. For example, in the former USSR, a paste formulation containing pine resin and placenta, known as Piktoin as an "active ingredient", is registered as an authorized penetrating agent through the sebaceous glands and partially through intracellular passages through the blood vessels. It is used in veterinary and human indications such as mastitis injuries, burns, traumatic tissue injury, eczema, dermitis ulcer and bruising injuries.

It is also known to use homemade blends containing pine resin and placenta as well as beekeeping end products (propolis, honey, pollen) to treat rheumatoid arthritis. Similar formulations are used for bone fractures and regeneration after joint surgery.

Composition of a natural substance marketed in the territory of the former Soviet Union eg:

% by weight of industrial white oil% by weight of beeswax% by weight of natural calcium carbonate% by weight of rosin

The viscosity of the product shows a significant dispersion (12002900 mPas), depending on the origin and time of collection of pine resin and beeswax.

It has been found that formulations of natural and proven medicinal resin and beeswax can stabilize the viscosity characteristics (regardless of origin and time of collection) of the formulation in the form of water-in-oil microemulsion ointments by selecting suitable pharmaceutical excipients.

Accordingly, the present invention relates to a process for preparing a water-in-oil microemulsion ointment having a viscosity of 600-4600 mPas. An ointment prepared by the process of the invention

17.5-22.5% by weight of pine resin,

17.5-22.5% by weight of beeswax,

wherein the total amount of pine resin and beeswax is 35-45% by weight, (1-1.3) :( 1,3-1) 35-55% by weight of the liposomal phase

- including

2.4 to 3.1% by weight of lecithin,

0.5-0.7% by weight of cholesterol,

37.5% to 47.5% by weight of the continuous liquid phase,

0.2-0.7% by weight of naturally occurring material (s),

4.5-5.5% by weight of the organic cosolvent phase

- within it, between 0,5 and 1,5% by weight of dimethylisosorbide as cosolvent,

2 to 4% by weight of naturally occurring material (s), with 1 to 3% by weight of polyethylene glycol (9) monododecyl ether as emulsifier, and

4-15% by weight of the aqueous phase

- including

2-3% by weight glycerol,

0.2 to 1% by weight of magnesium sulfate,

It contains from 2% to 11% by weight of water and the amount required for 100% by weight of other conventional excipients.

By varying the amount of water within a given range, the theological nature of the ointment - from flowing ointment to densely flowing ointment - can be varied.

The formulations may be prepared by adding to the liposomal phase a mixture of beeswax and pine resin heated to 55-65 ° C with stirring, followed by further mixing at 35-40 ° C with high shear mixing. At -25 DEG C., the aqueous phase is stirred until a consistency of ointment is obtained.

The ointments obtained were classified by determining the degree of dispersion and theological characteristics of the emulsions. An ointment film applied between a microscope object and a cover plate was used to characterize the degree of ornamental opacity.

The macroemulsion was detected with a Malverk 2600 laser particle size analyzer, while the microemulsion was detected with a Malverk Zeta 2C laser analyzer.

A dispersion in which the droplet size of the emulsion was 50% by weight greater than 1 μπι was considered a macroemulsion.

A dispersion in which the droplet size of the emulsion was 50% less than 700 nm was accepted as a microemulsion.

The viscosity characteristics of non-Newtonian Theological ointments were determined on a Rotovisko Haake RV 12 viscometer. The viscosity of the cut-off viscosity at D = 500 s' ^{1 was} considered as a rating characteristic.

The invention is illustrated by the following examples, without limiting the scope of the invention to the examples.

A. Preparation of the liposomal phase

To 0.3 g of eucalyptus oil and 0.2 g of peppermint oil were added 0.625 g of cholesterol and 3.0 g of lecithin, and the mixture was dissolved in 100 ml of chloroform.

The solution thus obtained is poured into a Rot rotary distillation vessel with a glass bead of diameter 1 mm. Chloroform was distilled off in the apparatus under vacuum at 25 ° C. The liposome adhered to the glass is dissolved in 50 g of white medicinal oil at 60 ° C. The liposomal solution was separated from the glass bead by a 0.5 sieve.

B. Preparation of Organic Cosolvent Dilution Phase A mixture of g of peppermint oil, 15 g of eucalyptus oil, 2.5 g of dimethyl isosorbide is prepared at 20 ° C. Then, while stirring, 10 g of menthol, 10 g of polyethylene glycol (9) monodecyl ether and 2 g of chlorophyll are dissolved in the mixture.

C. Preparation of the aqueous phase 7 g of magnesium sulfate are dissolved in g of distilled water with stirring. After complete dissolution, 20 g of glycerol is added to the solution.

Example 1 g of beeswax and 20 g of pine resin, and

HU 212 109 Β

50.05 g of liposomal phase A) is heated to 60 ° C and homogenized by stirring. The pure homogeneous phase is cooled to 40 ° C and 4.95 g of organic cosolvent phase B.) are added. The solution is cooled to 25 ° C and 5 g of the aqueous phase C) are added by high shear mixing with an Ultra-Turrax T45G homogeneous isomer. The products were microemulsion qualified by emulsion droplet size distribution and viscosity measurement as described.

The following examples illustrate the preparation of ointments prepared by the same procedure and qualification.

2-7. examples

Compositions% w / w

Example 2 3 4 5 6 7 * Beeswax 20 20 20 20 20 20 Rosin 20 20 20 20 20 20 Liposomal phase 47.55 45.05 42.25 40.05 52.55 37.55 Organic cosolvent phase 4.95 4.95 4.95 4.95 4.95 4.95 Aqueous phase 7.5 10.0 12.8 15.0 2.5 17.5 Water Conc. (%) 5.4 7.3 9.2 11.0 1.8 12.8 Viscosity (mPas) 2380 1835 1610 1080 4300 870 Type of emulsion We ointment We ointment We ointment Mi-Ma ointment We ointment Today ointment

8-13. example

example 8 9 * 10 * 11 12 13 Beeswax 17.5 16 22.5 24 17.5 22.5 Rosin 22.5 24 17.5 16 17.5 22.5 Liposomal phase 45.05 45.05 45.05 45.05 50.05 50.05 Organic cosolvent phase 4.95 4.95 4.95 4.95 4.95 4.95 Aqueous phase 10.0 10.0 10.0 10.0 10.0 10.0 Water Conc. (%) 7.3 7.3 7.3 7.3 7.3 7.3 Viscosity (mPas) 2710 4520 1235 640 795 2770 Type of emulsion We ointment We ointment Mi-Ma ointment Today ointment We ointment We ointment

Mi = microemulsion

Ma = macroemulsion * = comparative / off-line formulation

Claims (4)

Patent Claim Point Process for the preparation of a water-in-oil microemulsion ointment having a viscosity of 600-4600 mPas - which 17.5-22.5% by weight of pine resin, 17.5-22.5% by weight of beeswax, - where the total amount of pine resin and beeswax is 35-45% by weight, the ratio (1,3-1) :( 1-1,3) is 35-55% by weight of the liposomal phase - including 2,4- 3.1% by weight of lecithin, 0.5-0.7% by weight of cholesterol, 37.5-47.5% by weight of continuous liquid phase, 0.2-0.7% by weight of naturally occurring material (s), 4.5 to 5.5% by weight of the organic cosolvent phase, - within it, between 0,5 and 1,5% by weight of dimethylisosorbide as cosolvent, 2-4% by weight of naturally occurring material (s), 45 to 1% by weight of polyethylene glycol (9) monododecyl ether as emulsifier and 4 to 15% by weight of aqueous phase - including 2-3% by weight glycerol, 0.2 to 1% by weight of magnesium sulfate, 50 to 11% by weight of water and 100% by weight of other customary excipients, characterized in that beeswax and pine resin are added to the liposomal phase with mixing. The mixture was heated to 55-65 ° C, followed by co-solvent at 35-40 ° C with further stirring, then the aqueous phase under high shear stirring at 20-25 ° C, and the mixture was stirred until no consistent consistency ointment is obtained.