JPWO2019134982A5

JPWO2019134982A5 -

Info

Publication number: JPWO2019134982A5
Application number: JP2020528872A
Authority: JP
Publication date: 2022-01-13
Anticipated expiration: 2039-01-04

Claims

An oleogel comprising particles of about 1% to about 20% by weight of solid birch bark extract having an average particle size of less than about 50 μm and dispersed in one or more non-polar liquids .
The solid birch bark extract comprises at least about 70% by weight of bethulin and one or more triterpenes selected from the group consisting of betulinic acid, oleanolic acid, erythrodiol and lupeol.
a) The oleogel is sterile and / or
b) The consistency of the oleogel is in the range of about 300-3000 mN.
The consistency is the force [mN] required to penetrate 1 cm through the oleogel measured using a material tester (texture analyzer) equipped with a 1.27 cm cylindrical penetrating object, and the penetration velocity. Is 0.4 mm / sec, oleogel.

The oleogel according to claim 1, which is sterilized by ionization irradiation at a dose in the range of about 11 to about 40 kGy.

It has a consistency in the range of about 300-3000 mN, said consistency to penetrate 1 cm through an oleogel measured using a material tester (texture analyzer) equipped with a 1.27 cm cylindrical penetrating object. The oleogel according to claim 1, wherein the required force is [mN] and the penetration speed is 0.4 mm / sec.

The oleogel according to any one of claims 1 to 3, wherein the dispersed solid birch bark extract particles are the oleogel-forming agent in the oleogel, and no other oleogel-forming agent is present .

The oleogel according to any one of claims 1 to 4 , which comprises particles of the solid birch bark extract in an amount of about 10% by weight.

The oleogel according to claim 1, wherein the solid birch bark extract is dispersed in about 80% by weight to about 99% by weight of a non-polar liquid.

The oleogel according to any one of claims 1 to 6, wherein the non-polar liquid contains at least one C7 or more hydrocarbon.

The oleogel according to any one of claims 1 to 6, wherein the non-polar liquid contains one or more vegetable oils.

The oleogel according to claim 8 , wherein the non-polar liquid contains sunflower oil.

The oleogel according to any one of claims 1 to 9, wherein the oleogel is prepared by a method comprising dispersing a birch bark extract in one or more non-polar liquids, wherein the non-polar liquid is about 3. An oleogel having a peroxide value of less than.

The oleogel according to any one of claims 1 to 10 , wherein the oleogel substantially does not contain particles of a solid birch bark extract having a size exceeding about 50 μm.

The oleogel according to any one of claims 1 to 11 , wherein the oleogel is sterilized by ionization irradiation at a dose in the range of about 11 to about 20 kGy.

The oleogel according to claim 12, wherein the ionization irradiation is X-ray or gamma-ray irradiation.

The oleogel according to any one of claims 1 to 13 , wherein the separation of the non-polar liquid from the oleogel is less than about 10% after centrifugation at 2750 g for 30 minutes at 25 ° C.

Using a conical flat plate viscometer, Ph. Eur. When measured according to the rotational viscometer method described in 2.2.10, the viscosity of the oleogel at 200 / s is about 0.5 to about 4.0 Pa. In the range of s, the thixotropy value of the oleogel is about 200 to about 1200 Pa. The oleogel according to any one of claims 1 to 14 , which is in the range of s.

Sterilized wound dressing
(A) Pad and
(B) A sterile wound dressing comprising a therapeutically effective layer, comprising the oleogel of any one of claims 1-15 , disposed on at least one surface of the pad.

A solid birch bark extract comprising at least about 70% by weight bethulin and one or more triterpenes selected from the group consisting of betulinic acid, oleanolic acid, erythrodiol and lupeol.
(A) Contacting the birch bark with a pharmaceutically acceptable solvent to form an extract containing betulin and one or more triterpenes.
(B) Separation of the birch bark from the extraction solution and
(C) Cooling the extract so that a portion of the betulin and one or more triterpenes crystallize from the cooled extract.
(D) Separation of the crystallized betulin and one or more triterpenes from the cooled extract solution.
(E) Prepared by a method comprising drying the separated crystallized betulin and one or more triterpenes to provide the solid birch bark extract.
After drying, the dry solid birch bark extract of about 1% by weight to about 20% by weight of the step (e) dispersed in the refined sunflower oil forms an oleogel, which is a solid birch bark extract.

A method for preparing a solid birch bark extract containing at least about 70% by weight of bethulin and one or more triterpenes selected from the group consisting of betulinic acid, oleanolic acid, erythrodiol and lupeol.
(A) Contacting the birch bark with a pharmaceutically acceptable solvent to form an extract containing betulin and one or more triterpenes.
(B) Separation of the birch bark from the extraction solution and
(C) Cooling the extract so that a portion of the betulin and one or more triterpenes crystallize from the cooled extract.
(D) Separation of the crystallized betulin and one or more triterpenes from the cooled extract solution.
(E) Containing the drying of the separated crystallized betulin and one or more triterpenes to provide the solid birch bark extract.
After drying, about 1% by weight to about 20% by weight of the dry solid birch bark extract of step (e) dispersed in the refined sunflower oil forms an oleogel.
A method for preparing a solid birch bark extract .

One or more steps (a), (c), and (e) have the following conditions:
(I) The contact of step (a) is carried out at a temperature of about 60 ° C to about 130 ° C;
(Ii) The cooling of step (c) is carried out at a temperature of about −20 ° C. to about 35 ° C.;
(Iii) The solid birch bark extract according to claim 17, wherein the drying of step (e) is carried out at a pressure of less than about 70 mbar and a temperature of about 75 ° C to about 95 ° C. Method.

Two or more steps (a), (c), and (e) have the following conditions:
(I) The contact of step (a) is carried out at a temperature of about 60 ° C to about 130 ° C;
(Ii) The cooling of step (c) is carried out at a temperature of about −20 ° C. to about 35 ° C.;
(Iii) The solid birch bark extract according to claim 17, wherein the drying of step (e) is carried out at a pressure of less than about 70 mbar and a temperature of about 75 ° C to about 95 ° C. Method.

Steps (a), (c), and (e) have the following conditions:
(I) The contact of step (a) is carried out at a temperature of about 60 ° C to about 130 ° C;
(Ii) The cooling of step (c) is carried out at a temperature of about −20 ° C. to about 35 ° C.;
(Iii) The solid birch bark extract according to claim 17, wherein the drying of step (e) is carried out at a pressure of less than about 70 mbar and a temperature of about 75 ° C to about 95 ° C. Method.

The solid birch bark extract or method according to any one of claims 17 to 21, wherein the sunflower oil has a peroxide value of less than about 3.

The solid birch bark according to any one of claims 17 to 22, wherein the pharmaceutically acceptable solvent is a hydrocarbon selected from the group consisting of n-pentane, n-hexane, or n-heptane. Extract or method.

One of claims 17-23 , wherein the pharmaceutically acceptable solvent is n-heptane and the contact is carried out at a temperature of about 115 ° C to about 130 ° C for about 8-12 minutes. The solid birch bark extract or method according to.

The solid birch bark extract or method according to any one of claims 17 to 24 , wherein in step (c) the cooled extract solution is supersaturated at least about 2-fold or about 5-fold .

The solid birch bark extract or method according to any one of claims 17 to 25 , wherein the amount of the residual extraction solvent is about 0.5% by weight or less.

An emulsion containing the solid birch bark extract according to any one of claims 17 or 19 to 26 .

An emulsion containing the oleogel according to any one of claims 1 to 15 .

A foam containing the emulsion according to claim 27 or 28 .

A pressurized container filled with a mixture containing the emulsion according to claim 27 or 28 and a pharmaceutically acceptable propellant, when decanting at least a portion of the mixture from the container. , A pressurized container in which the emulsion forms a foam.

A composition for treating a patient's wound by topical administration to at least a portion of the wound, comprising the oleogel according to any one of claims 1-15 .

The wounds are burns, surgical skin lesions, body surface injuries, chronic wounds, decubitus, diabetic foot ulcers, chronic venous ulcers, arterial insufficiency ulcers, aesthetic skin treatment wounds, ablation laser skin treatment wounds, chemical peeling. Wounds caused by skin peeling, wounds caused by side effects of drugs, wounds caused by toxic epidermal necrosis, wounds caused by Riel syndrome, wounds caused by Stevens Johnson syndrome, and wounds caused by radiation-induced dermatitis. 31. The composition of claim 31 selected from.

A composition for treating a patient's wound by topical administration to at least a portion of the wound, comprising the emulsion of claim 27 or 28 .

A composition for treating a patient's wound by topical administration to at least a portion of the wound, comprising the foam of claim 29 .

The composition for treating epidermolysis bullosa in a patient who requires it by topical administration to the area of epidermolysis bullosa in the patient , according to any one of claims 1 to 15. A composition comprising oleogel .