JPS6022682B2 - ointment base - Google Patents

Description

[Detailed description of the invention] The present invention relates to stable oleaginous ointment bases.

In recent years, pharmaceutical ointments have become highly effective, safe, and sensually superior; one reason for this is the ointment base (hereinafter sometimes abbreviated as base) that makes up the ointment. It is said that ointments have made remarkable progress, coupled with the emergence of new drugs and the development of formulation technology. There are various types of ointments, and if they are schematically classified, they can be roughly divided into the following categories.

Water-soluble ointment: An ointment made by adding an acid-reducing substance to a hydrophilic base containing a water-repellent substance dispersed in soot, such as ``toothpaste.''

o Emulsion ointment: An emulsion based on water, oil, and a surfactant that is emulsified into an oil-in-water or water-in-oil paste, with vanishing cream being an example of the former, and cold cream being an example of the latter. .

Ointments based on these are supplemented during the manufacturing process of the base. C. Oil-based ointment: A base containing a water-insoluble oil-based substance as a dispersant, and the base is hydrophobic, to which the main drug and other dispersoids are added.

The cartilage base of the present invention is applied to ointments that fall into category C of the above A to C, but specifically, liquid paraffin (hereinafter abbreviated as liquid paraffin) is a component. include. It is applied to petroleum-based base materials. The general characteristics of the petroleum base are summarized as follows. In other words, this base material is an important base material with a long history, and the reason for this is that petroleum-based substances are available in many varieties with different physical properties such as viscosity, hardness, color tone, and chemical composition. This is possible, and since the quality of these products is almost constant for each variety, the master can freely obtain the desired variety and prepare the desired base without worrying about quality. : Also, the base has high chemical and physical stability, and has little interaction with the drugs it is mixed with; and it is physiologically inert when applied to the affected area and has no effect on the living body. For example, it has good drug release properties.

Although this base has many advantages, it is not without its drawbacks. This will be explained in a little more detail as follows. '1' The simplest example of an ointment base that can be cited as a disadvantage of petroleum-based ointment bases in the prior art is petroleum-based laxatives that are stable at room temperature, such as vaseline and microcrystalline wax (hereinafter referred to as micro-W). It is a base made by heating and melting solid paraffin, etc., alone or in combination.

The hardness of the base material changes greatly depending on the external environmental temperature (hereinafter simply referred to as temperature), and the composition of the base material at room temperature is not homogeneous, with wax crystals simply being dispersed in the liquid. First, the smaller the amount of vaseline prescribed, the more time-consuming changes will occur within a short period of time, and separation of fluids will be inevitable. In order to prevent such separation, compromises with the prior art ointment bases listed in item (2) below are attempted, but it is difficult to expect perfect performance. (2) Add about 10% of soft silicic anhydride or other fine particle powder to the liquid and form it into a paste to use as a base.

Although the base material has changes such as a small change in steeliness with respect to temperature, flow separation cannot be avoided even by, for example, a compromise with the ointment of the conventional technique described in {1} above. This separation is noticeable when the preparation is low and decreases when the preparation is high, but what is more important is that the release of the drug in the affected area is suppressed by the influence of the dispersoid, and therefore the ointment base is also Moreover, it is not necessarily a satisfactory base. '3} In order to improve the drawbacks of the ointment base of the sub-techniques described in {1} and [2] above, low weight polyethylene or aluminum salts of higher fatty acids, etc. are added to Narupara and dissolved by heating to around 150 qo. A base obtained by cooling and then quenching is in practical use.

A typical example is the former (polyethylene), which is called Plastibase (trade name of an ointment base manufactured by Squibb Company in the United States), and has already been used in more than 20 cases around the world. Although this base satisfies most of the above-mentioned excellent characteristics of petroleum-based bases, the only drawback is that it is not as good as other conventional petroleum-based bases (although to a lesser extent). Slight separation of the flow rate is unavoidable, and may be noticeable especially if heat management in the manufacturing process is incomplete. Furthermore, the base polyethylene forms a stable matrix within the ryupara, thickening the ryupara into a paste-like consistency, and this matrix cannot be overflowed to more than 60 qo or subjected to continuous mechanical force. The essential drawback is that if the polyethylene is used, it will lose its homeostasis, the polyethylene will coagulate, and the liquid will completely separate. Therefore, not only heat sterilization but also combinations with drugs that dissolve when heated, and lengthy polishing processes are contraindicated. ．． or more (1
1 - [Common shortcomings of the prior art ointment bases that can be applied immediately can be summarized as ``separation''.

The present inventors studied the composition of a mixture of Ryupara and Micro W in order to obtain a base that does not cause any separation while taking advantage of the characteristics of the petroleum base described above.

That is, the base obtained by heating and melting Ryupara and Micro W and then cooling it is a transparent, fine-textured paste-like base that is excellent both in appearance and sensuality. } As mentioned above, the disadvantages were the large change in steel hardness with temperature and the unavoidable separation of flow particles.
Therefore, the present inventors applied the ointment base described in ``2'' above to counter these problems, but adding light silicic acid anhydride increased the steel strength and was able to prevent separation to a certain extent, but the opposite effect occurred. It was judged that this was inconvenient in the manufacturing process because there was little decrease in steel strength even if it was flooded with water. Next, the present inventors conducted research to search for a substance that melts under heat and then cools down to form a stable base at room temperature, as described in technique (3) above. The substance is dextrin fatty acid ester (
(hereinafter abbreviated as OFA) (preferably Kaiha Kagaku KK (trade name: RheopeariKE)), and completed the present invention. Furthermore, even if petrolatum is used instead of Micro-W, an ointment base can be obtained that does not cause separation of petrolatum and petrolatum due to the addition of the above-mentioned DFA, which is a feature of the present invention.

Regarding the chemical nature of Micro-W and petrolatum, both Micro-W and petrolatum are mixtures of non-flowing hydrocarbons obtained from petroleum, but the former is a fine crystalline solid (a flexible lump). On the other hand, the latter is semi-solid (paste-like) and amorphous. Minimum addition rate of DFA to achieve prevention of separation of liquid substance from the composition when the composition ratio of Narupara to Micro W and the composition ratio of Narupara to Vaseline are 3:1, 2:1, and 1:1 were measured and the results shown in Table 11 were obtained.

Table-1 Composition ratio and addition rate of DFA Ryupara, DFA and Mike.

In the mixture of W, the steel strength is as follows: Flow Para and Micro W
Micro W in the composition has the role of imparting "stickiness". From the results in Table 1, D according to the present invention
FA addition is used for the purpose of preventing separation, but for example, when the flow is semi-fluid at 20 pm, Micro W
In the case of =3:1, 2% of DFA is required for the purpose, and similarly, the ratio of DFA to be used as an ointment at 20 pm C: Mike. It can be seen that in the case of W=1:1, the objective can be achieved by adding 1%. The present invention can also be applied when petrolatum is used instead of Micro W, and the effect of adding DFA when using petrolatum is not as significant as the effect of adding DFA when using Micro W). Prevention of segregation can also be achieved by adding DFA.

From Table 1, a 3:1 mixture of ryupara and petrolatum is 20
oo is in a semi-liquid state, and DFA added to prevent separation in this case is ineffective at less than 5%, and at least 6% DFA is added to prevent separation.
For a 1:1 mixture with vaseline, an addition of 2% is necessary to achieve the objective. That is understood. The effect of adding DFA according to the present invention (ie, the effect of preventing separation of liquid substances from the ointment base composition) was demonstrated as follows.

That is, three types of samples A, B, and C of the compositions of flow puff, Micro W, and DFA shown in Table 1 and their respective controls (DF
For A), place each magazine material in a beaker with a capacity of 50 volumes, scrape off the center of the spatula in a conical shape, and form a recess (conical cavity) in the beaker, with the top of this cone reaching the bottom of the beaker. , so that the edge of the conical pond reaches near the upper edge of the beaker, and after leaving it in the 370 thermostat for a certain period of time, place the warming beaker in it, separate it, and pour out the liquid substance that has accumulated in the recess into the watch glass. , and the results shown in Table 2 were obtained. Table 2 Amount of liquid substance separated (phosphorus) The characteristics of the base of the present invention are summarized below.

{1} Based on chemically stable and physiologically inert substances such as Ryupara and Micro W.

'2} In either case, whether it is an ointment base as it is, an ointment with a few percent or less of a drug added, or a pasta preparation made by adding appropriate powder, the stability against temperature is Separation does not normally occur under the conditions in which pharmaceutical products are stored.

'3- The composition of the ointment base is Ryupara, Micro W and D.
It is a simple three-component of FA, and if you reduce the amount of Micro W that has increased flow parameters, the steeliness will decrease; if you do the opposite, the steeliness will increase and "stickiness" will appear, and if you increase the amount of DFA, the steelness will decrease. Since the hardness increases, it is possible to select any blending ratio to obtain a desired ointment base.

'41 The above three components of the ointment base are
Since the base material can be prepared by simply flooding the base material to 0 and cooling it to room temperature, heat management is easy, and the heating-melting-cooling-solidification process is reversible.

Therefore, the base material can be sterilized. [51] Since there is no interaction with the compounded drug and the drug release property is good, the drug release property from the ointment to the living body side is good.

'6} The base ingredients are simple, heat management is easy, and the manufacturing equipment is simple, so the cost is low, and conventional equipment can be used as is. The following two points can be highlighted regarding the use of the soft tube base of the present invention: [a] The base obtained according to the present invention can be used in ointments using conventionally used hydrophobic petroleum bases. Applied to, for example, synthetic wealth.

It can be applied as a base for corticosteroid ointment and eye ointment that requires heat sterilization. [b- A base material with a low steel content can be easily obtained, and the base material not only does not have its homeostasis damaged by mechanical operations such as kneading or grinding, but also has a low steel content. Since blending with gelatin, CMC sodium, sodium polyacrylate, dextrin, etc. is not contraindicated, these powders (sticky powders) may be kneaded alone or in combination of two or more to a concentration of 40 to 50%. By adding antibiotics, bactericidal agents, oxygen, and various hormones to the softened pasta, it can be applied as a so-called oral pasta preparation, which is applied to the oral mucosa and adhered to the oral mucosa at the time of use.

Next, embodiments of the present invention will be explained with reference to Examples, but these Examples are merely illustrative and do not limit the present invention.

Example 1 Ryūpara (manufactured by Domestic Chemical KK, specific gravity 0.855 or more) 1.5
DFA30 and Micro W (manufactured by Sonneborn, USA) 1.0k9 were added to k9, and the mixture was heated in a steam bath at 100°C to allow it to melt evenly, and then the pore size was 3A.
Filter through a furnace and cool to room temperature.

During the cooling process, the mixture is dispensed into suitable containers and used as an ointment base, or sold commercially. Example 2 Ryu Para (same as used in Example 1) 1.0k9
DFA40 and Vaseline (Japanese Pharmacopoeia) 1.0k9
The mixture was heated at a steam rate of 100 oo, heated in the same manner as in Example 1, and used as a base for an ointment or sold commercially.

Matters related to the present invention will be described below. 1 For a mixture of liquid paraffin and non-flowing mineral wax,
Add a small percentage of dextrin fatty acid ester, about 100
1. A method for producing a stable ointment base, which is obtained by uniformly melting the entire material at a temperature of 1:00 pm and then cooling it.

Claims (1)

[Scope of Claims] 1. A stable ointment base comprising the following three components: (a) liquid paraffin, (b) non-liquid mineral oil wax, and (c) dextrin fatty acid ester. 2. The stable ointment base according to claim 1, wherein the non-flowing mineral oil-based wax is a microcrystalline wax. 3. A stable ointment base according to claim 1, wherein the non-flowing mineral oil-based wax is petrolatum. 4. A stable ointment base according to claim 2, in which at least 1% by weight of dextrin fatty acid ester is added to the content of liquid paraffin and microcrystalline wax. 5. A stable ointment base according to claim 3, in which at least 2% by weight of dextrin fatty acid ester is added to the content of liquid paraffin and petrolatum.