CH639869A5 - Process for preparing a biologically active gel - Google Patents

Description

The present invention relates to a method for producing a biologically active gel.

The process according to the invention for producing a biologically active gel is characterized in that, in order to accomplish the gelatinization, a feed solution is treated which contains an inorganic species and a biologically active component which is active or becomes active in use, so that an inorganic gel is formed by a sol-gel conversion and thus a biologically active gel is produced which contains the biologically active component which is active or becomes active when used, distributed over the inorganic gel.

“Biologically active component” is to be understood as a component which contains a biological activity in a selected environment and which is active or becomes active when used; “Biologically active gel” should be interpreted in such a way that it means a gel that contains an active component, as mentioned above. Thus, for example, the component may be a pharmaceutically active component so that the active gel is a pharmaceutically active gel (ie, a pharmaceutical gel), or the active component may be a pesticide, in which case the active gel will have pesticidal activity . On the other hand, for example, a herbicidal gel can be prepared by incorporating a herbicide as an active component. Another possibility is that the active component is a toxin that grows in an environment of water

40 inhibits (e.g. to curb the growth of water weeds or molluscs), the active gel can be used in marine paints against pollution. As a further possibility, the active component can be an algicide, so that the gel has an algicidal activity.

In accordance with a preferred embodiment of the present invention, there is obtained a method of making a pharmaceutical gel. This is characterized in that a starting solution, which contains an inorganic species and a pharmaceutically active component, is treated to carry out the conversion into a gel, so that an inorganic gel is formed, and a pharmaceutical gel is thus produced, which contains the pharmaceutical component , 55 which is distributed over the inorganic gel.

It is recognized that the inorganic species in the starting solution may be, for example, in the form of a colloidal dispersion (sol) or a salt solution with anions deficiency or a mixture thereof.

6o The sol-gel conversion can be carried out according to known methods. An example of this is the concentration of inorganic species through drainage.

Usually the inorganic species can be an inorganic compound or a mixture of inorganic compounds (e.g. A1203, Al203 / Mg0 or Al203 / Si02); Usually, the preparation of the starting solution can include the step of mixing a solution or a sol of the inorganic component or of the inorganic component

Contain components with the active compound or a solution thereof.

Preferred is the gel which is an oxide, a water-containing oxide or a hydroxide, particularly preferred the inorganic gel is an oxide, a water-containing oxide or a hydroxide of aluminum oxide.

In the process according to the invention, the inorganic gel is obtained by gelatinizing a colloidal solution (i.e. by means of a “sol-gel” process).

The invention is not restricted to gels which contain only an inorganic gel and an active component, since further additives can be introduced.

Thus, in one embodiment of the process according to the invention, the starting solution can likewise contain a polymeric substance, so that the gel product contains an inorganic gel, a polymeric organic substance and a biologically active component (for example a pharmaceutically active component).

For example, the polymeric organic substance may be a substance that can be used as an "organic gelling agent" (sometimes called a "gelatinizing agent") in the gel precipitation process. Such organic gelling agents are usually water-soluble, high molecular weight polymeric organic compounds (e.g., dextran, polyvinyl alcohol, dextrin and starch). British Patents Nos. 1 175 834.1 231 385.1 253 807, 1 313 750 and 1 363 532 relate to gel precipitation procedures and reference is made to these publications for information purposes about such procedures.

Attention should also be drawn to related, also pending British Application Nos. 32 970/76 and 46 496/76, which disclose inter alia the use of polymeric organic substances in the manufacture of active gels (e.g. pharmaceutical gels).

In one embodiment e.g. the starting solution (optionally containing a polymeric organic substance as reported above) can be spray dried to give substantially spherical active gel particles (e.g. particles of a pharmaceutically active gel).

In another embodiment, the starting solution can be freeze-dried to produce an active gel.

In a further embodiment, the starting solution can be subjected to dewatering with an organic solvent, the starting solution being brought into contact with an organic liquid which is able to extract the water from the starting solution to form an active gel.

In an additional embodiment, the starting solution can be dried by azeotropic distillation.

Reference is made to British Patent No. 1419 492 in connection with dewatering with an organic liquid and with azeotropic distillation.

It is understood that when using organic drainage or azeotropic distillation, the biologically active component (e.g. the pharmaceutical component) should have a low solubility in the organic liquid.

If droplets are formed from the starting solution during organic dewatering or azeotropic distillation, a special gel product can be obtained.

To form a gel, other common methods of accomplishing gelatinization can be used in the practice of the present invention. For example, one can use the ion exchange in the liquid

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(An example of an ion exchange in the liquid is where ions are removed from a solution or a gel [for example, nitrate ions can be removed by using "Primene JMT" in a solvent selected for this]).

Another aspect of the present invention relates to the preparation of an active gel which contains an active component which is distributed over an inorganic gel, said inorganic gel being formed by a sol-gel conversion.

The biologically active component is preferably a pharmaceutically active component, so that the active gel is a pharmaceutically active gel.

A pharmaceutically active gel is preferred in the form of essentially spherical gel particles, which are customary in patients owing to the simple handling and administration. This can be achieved by converting the starting solution into droplets before the inorganic gel is formed.

Substantially spherical pharmaceutical gel particles in accordance with the present invention can range in size from several microns to several millimeters. In the case of a pharmaceutical gel, small particles (i.e. 1-1000 microns) can be administered orally with capsules, while larger particles (i.e. 1-5 mm) can be administered orally individually.

In accordance with another aspect of the present invention, a method of making an active gel arises. This is characterized in that a starting solution which contains an inorganic species and a pharmaceutically active component is treated for the purpose of gelatinization, so that an active gel is formed which contains the active component which is distributed over the inorganic gel, wherein the structure of the gel is used to determine the rate at which the active component is released from the gel for use.

A preferred embodiment of the immediately aforementioned aspect of the present invention relates to a process for the preparation of a pharmaceutical gel, in which a starting solution which contains β-inorganic species and a pharmaceutically active component is treated to carry out the gelatinization so that a pharmaceutical gel is formed, which is distributed over the inorganic gel, in which the structure of the gel is controlled in order to determine the rate at which the active component is released when the gel is administered to a patient.

The structure of the gel, and hence the rate at which the active component is released, can be determined by modifying the composition of the starting solution, thereby changing the composition of the active gel. Thus, an additional inorganic compound can be contained in the starting solution to modify the composition of the gel. (Examples of inorganic compounds which are suitable for use as additives in connection with the embodiment just mentioned are silicon dioxide and pyrrolytic aluminum oxide).

The structure of the gel can be controlled; consequently, it is possible to determine the rate of release of the active component by the choice of the gelatinization process by which the inorganic gel is to be formed. In certain cases it is also assumed that the structure of the gel is influenced by treatment of the gel after its formation and that the rate of release can thus be determined. It is believed that the speed3

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The rate at which the active component is released depends on a number of factors. These are:

a) pH of the medium (e.g. stomach, intestine in the case of a pharmaceutically active gel),

b) size of the gel particles,

c) chemical composition of the inorganic gel,

d) porosity of the gel,

e) crystal size and structure of the inorganic gel,

f) water content of the gel,

b) affinity of the gel for water (hydrophilic nature),

h) the presence or absence of a polymeric organic substance; it is believed that this can be particularly important if the polymeric organic substance partially forms complexes with the inorganic gel.

The rate of release in a given case is expected to be a complex function from all of the above factors.

It is believed that the rate of release is affected by the extent to which water is removed from the starting solution, the temperature at which gelation is performed, and the components selected in the starting solution (e.g. sol, dispersion, or brine with anions) - deficit or the chemical composition [eg Si02 or A1203]).

In accordance with a further aspect of the invention, an active gel is obtained which has been produced by the process according to the invention.

In accordance with an additional aspect of the present invention, an active gel is created which has been acted upon to determine the rate at which the active component is released from the gel for use.

In a preferred embodiment of the instantly stated aspect of the present invention, a pharmaceutically active gel is created, the structure of which is controlled to thereby determine the rate at which the pharmaceutically active component is released from the gel when administered to a patient he follows.

It is believed that pharmaceutically active gels which can be produced according to the invention have advantages over conventional tablets 10 and capsules with regard to the uniformity of the distribution of the pharmaceutically active component over the pharmaceutically active gel and to the concentration of the pharmaceutically active component obtainable in the gel.

A pharmaceutical composition is also obtained which contains a pharmaceutically active gel which can be prepared according to the invention and which is admixed with a pharmaceutical carrier which is compatible with it.

To prepare a pharmaceutical composition, a pharmaceutically active gel produced according to the invention can be mixed with a compatible pharmaceutical carrier.

A treatment method may include administering a therapeutic dose of a pharmaceutically active gel made in accordance with the invention.

The following example is now given for explanation.

example

100 g of dispersible boehmite, which was prepared according to the description of British Patent No. 1 174 648, was dispersed in 500 ml of distilled water, which contained 1.0 g of imipramine hydrochloride. The resulting mixture was spray dried to form a predominantly spherical powder with good flow properties. The imipramine hydrochloride was released in 35 normal salt solutions within five minutes.

Claims (8)

639869 2nd PATENT CLAIMS 1. A method for producing a biologically active gel, characterized in that, in order to bring about gelatinization, a starting solution is treated which contains an inorganic species and a biologically active component which is active or becomes active when used, so that an inorganic gel arises from a sol-gel conversion and thus a biologically active gel is produced which contains the biologically active component which is active or becomes active when used, distributed over the inorganic gel. 2. The method according to claim 1, characterized in that the biologically active component is a pharmaceutically active component, a pesticide, a herbicide, a toxin which is capable of inhibiting growth in an aqueous environment, or an algicide, each of these substances being the use is active or becomes active. 3. The method according to any one of claims 1 to 2, characterized in that the inorganic species is present in the starting solution in the form of a colloidal dispersion (sol) or a salt solution with anion deficit or a mixture thereof. 4. The method according to any one of claims 1 to 3, characterized in that the inorganic species is an inorganic compound or a mixture of inorganic compounds. 5. The method according to any one of claims 1 to 4, characterized in that the inorganic gel is an oxide, a water-containing oxide or a hydroxide. 6. The method according to any one of claims 1 to 5, characterized in that the starting solution also contains a polymeric organic substance. 7. The method according to claim 1, characterized in that the starting solution for generating an active gel of an organic drainage by contact with an or- s ganic liquid is subjected, which can extract water from the starting solution. 8. The method according to claim 1, characterized in that the starting solution is dried by azeotropic distillation. 9. Process according to claim 7 or 8, characterized in that the starting solution is converted into droplets during the organic dewatering or the azeotropic distillation, so that a special gel product is obtained. i5 10. The method according to any one of claims 1 to 9, characterized in that the structure of the gel by a) selecting the gel binding process or b) checking to what extent water is removed from the starting solution, or 20 c) the selection of the components in the starting solution in order to control the chemical composition and / or the physical characteristics of the gel, or d) the control of those achieved during gelatinization 25 th temperature or by any combination of a) to d), is affected to determine the rate at which the biologically active component is released from the gel for use. 30th