JPH04270215A - Transvaginal or transrectal administration composition - Google Patents

Abstract

PURPOSE:To obtain a new sustained-release transvaginal or transvaginal administration composition. CONSTITUTION:A transvaginal or transrectal administration composition consisting of a medicine, a gum derived from a plantago plant and a base material. The gum is a sustained release constituent and performs slow release of medicines without mutually acting with medicines or base materials, is safe to living bodies and does not stimulate mucous membrane. Production of the composition does not become complicated one by adapting such a gum as a sustained release constituent. As a result, in the composition of the present invention, kinds of medicines and base materials used are not limited.

Description

[Detailed description of the invention]

0001

FIELD OF THE INVENTION This invention relates to the field of pharmaceutical compositions, particularly sustained release vaginally or rectally administered compositions.

0002

[Prior Art] Compositions for vaginal or rectal administration, such as suppositories and rectal capsules, have a low rate of drug decomposition in vivo, and can be easily administered not only to children and the elderly, but also to patients who cannot take oral administration. It is a dosage form that has recently been used because it is not affected by food, etc. However, on the other hand, it has been pointed out that there are drawbacks to administering drugs vaginally or rectally, such as the risk of side effects due to a rapid rise in plasma concentration and the difficulty of administering drugs multiple times a day. Various attempts have been made in the past to solve these drawbacks by providing sustained release formulations. In most cases, sustained release is achieved by incorporating specific formulation ingredients. For example, JP-A-58-1
40012 is ethyl cellulose, 62-2465
No. 16 uses surfactant, No. 62-149628 uses collagen, No. 63-183523 uses hydrogenated phospholipid, No. 63-14716 uses hydrogenated lecithin, and JP-A-1-63512, No. 1-110618, No. 2- 730
In No. 10, sucrose fatty acid ester, in No. 2-15024, minerals such as montmorillonite, and in No. 2-36123, sodium alginate were used as formulation ingredients for sustained release (hereinafter sometimes referred to as sustained release ingredients). It is used.

[0003] However, sustained release using these formulation ingredients is not always satisfactory. For example, hydrogenated lecithin, which is a sustained-release ingredient, cannot coexist with a water-soluble base, and there are also concerns that it is unstable, and when using sodium alginate, there are concerns about the reactivity of these with drugs and bases. There are problems such as.

0004

[Problems to be Solved by the Invention] The problems to be solved by the present invention are to obtain a reliable sustained release effect without interacting with drugs or bases, to be safe for living organisms, and not to irritate mucous membranes; Another object of the present invention is to find a new sustained-release component that does not complicate the production process of the target composition for vaginal or rectal administration.

[0005]

[Means for Solving the Problems] The above problems can be solved by the present inventors if they select a gum derived from the Plantago plant as an ingredient for achieving sustained release of compositions for vaginal or rectal administration. The present invention was completed based on this knowledge.

[0006] Plantago plants are annual plants of the progenitor family that are mainly cultivated in India. As a plantago plant, Plantago ovata (P. ovata)
is the most famous, and other plants such as P. indica, P. arenaria, and P. psylium are also known. Plantago plants, especially their seed coat (husk)
Gum derived from psyllium (sk) is derived from psyllium
) or Isapgol, D
- It is a polysaccharide whose main constituents are xylol and L-arabinose, and has various properties such as being water-swellable and edible, but not absorbable in the living body. When taken, gum derived from the plantago plant stimulates intestinal peristalsis in the intestines, so it has been used as a laxative since ancient times, and more recently as a slimming agent (health food), and its safety for living organisms has already been established. There is. However, this gum has never been used as one of the formulation ingredients in a composition for vaginal or rectal administration.

The present invention relates to a sustained-release vaginally or rectally administered composition comprising a drug, a plantago plant-derived gum, and a base.

[0008] The drug in the composition of the present invention may be water-soluble, poorly water-soluble, heat unstable, or any other property, and its type is not particularly limited.

[0009] Also, the type of base in the composition of the present invention is not particularly limited, like the drug, and any of the conventionally used oil-based bases, water-soluble bases, and emulsifiable bases can be used. Available for use. Examples of the oleaginous base include mixtures of higher fatty acid triglycerides/diglycerides/monoglycerides [for example, various Witepsol (Hürtz), various Novata (Henkel), various Pharmasol (Nippon Oil), isocacao (Kao), Supporter (
Gutfords)] and medium chain fatty acid triglycerides [
For example, Miglyol (Dynamite Nobel)
Examples include glycerin fatty acid ester, cacao butter, hydrogenated oil, corn oil, liquid paraffin, and petrolatum. Examples of water-soluble bases include polyethylene glycol, propylene glycol, glycerin, and gelatin. As the emulsifying base, polyoxy(40) stearate [for example, Nikkor MYS-40 (Nikko Chemicals)
] can be given. These bases may be used alone or in the form of a mixture.

[0010] A preferred example of the gum derived from the Plantago plant is the gum derived from the end of the seed coat of Plantago lobata, and a fine powder, specifically one that can pass through a 100 mesh sieve, is preferred. In addition, auxiliary ingredients such as surfactants, absorption enhancers, and mucosal protectants may be added as necessary.

In the composition of the present invention, the gum derived from the Plantago plant accounts for 50% by weight or less, preferably 2-30% by weight, particularly preferably 5-20% by weight, and the drug accounts for 2% by weight.
It accounts for 5% by weight or less, and the remainder is occupied by the base and other auxiliary ingredients.

The composition of the present invention may be in the form of suppositories, rectal capsules, or ointments. The ointment is administered using a special syringe.

The composition of the present invention is basically produced by dissolving or dispersing the drug in a base and dispersing therein a gum substance derived from the Plantago plant. Suppositories can be produced by melting a base that is solid at room temperature at about 70°C or lower, preferably 40-60°C, blending the necessary ingredients therein, pouring the mixture into a container, and cooling it. Rectal capsules are generally produced by blending the necessary ingredients with a liquid base such as Miglyol and filling the mixture into gelatin soft capsules. Ointment-like compositions are manufactured by blending the necessary ingredients into a base such as liquid paraffin or petrolatum. In either case, auxiliary ingredients are generally combined with the drug. It is considered that most of the gum derived from the Plantago plant in the composition is dispersed as a solid.

[0014]

[Examples] The present invention will be explained in more detail with reference to Examples and Comparative Examples below. In the following examples and comparative examples, 1
A gum substance derived from the end of the seed coat of Plantago lobata (hereinafter also referred to as gum substance) that had been passed through a 00 mesh sieve was used. In addition, in the following formulations, the amount of each ingredient contained in one suppository or rectal capsule is indicated.

Example 1-3 Witepsol H-15 as an oleaginous base was heated at 42-45°C.
Sodium valproate and a gum substance were dispersed therein according to the recipe shown in Table 1, and this was filled into a suppository container and cooled to obtain a suppository.

[0016]

[Table 1]

Example 4 Sodium valproate
300mg
gum quality
120mg Novata 299 780m
g ──────────────
────────── All
Amount 120
Novata 299, which is a 0 mg oleaginous base, was melted at 42-45°C, and sodium valproate and gum were dispersed therein, which was then filled into a suppository container and cooled to obtain a suppository.

Example 5 Sodium valproate
300mg
gum quality
120mg cocoa butter 780
mg ────────────
────────── Total amount
1200 mg of cacao butter as an oily base was melted at 42-45°C, and sodium valproate and gum were dispersed therein, which was filled into a suppository container and cooled to obtain a suppository.

Example 6 Sodium valproate
300mg
gum quality
120mg Miglyol 810 780mg
────────────────────
──── All
Amount: 1200 mg Sodium valproate and gum were dispersed in Miglyol 810, which is an oily base, and this was filled into gelatin soft capsules to obtain rectal capsules.

Example 7 Sodium valproate
300mg
gum quality
120mg Nikkor MYS-40 780mg
────────────────────
─── Total amount: 1200 mg Nikkor MYS-40, which is an emulsifying base, is melted at 50-60°C, sodium valproate and gum are dispersed therein, and this is filled into a suppository container, cooled, and made into a suppository. obtained the drug.

Example 8-10 Polyethylene glycol 4000 and polyethylene glycol 6000 as water-soluble bases were melted at 60-70°C, indomethacin was dissolved in the base according to the recipe shown in Table 2, and a gum substance was further dispersed. This was filled into a suppository container and cooled to obtain a suppository.

[0022]

[Table 2]

Example 11 Indomethacin
50mg
gum quality
120m
g polyethylene glycol 4
00 530mg
Propylene glycol
500mg ─
────────────────────────
Total amount
120
0mg Polyethylene glycol 40 as water-soluble base
0 and propylene glycol were mixed, indomethacin was dissolved therein, and a gum substance was further dispersed, and the mixture was filled into gelatin soft capsules to obtain rectal capsules.

[0024]

[Effects of the Invention] The composition for vaginal or rectal administration of the present invention contains a gum derived from the Plantago plant as a sustained-release component, and this gum does not interact with the drug or the base. It aims to achieve sustained release of drugs without causing any harm, is safe for living organisms, and does not irritate mucous membranes. Further, by employing such a gum substance as a sustained release component, the method for producing the composition does not become complicated. Therefore, the types of drugs and bases used in the compositions of the present invention are not limited. The sustained release effect of the composition of the present invention will be explained below using experimental examples.

Experimental Example 1 Release experiments of sodium valproate from the suppositories obtained in Examples 1-3 and the suppositories of Comparative Example 1 were carried out using the dissolution test method (rotating basket method) described in the Japanese Pharmacopoeia 11th edition. I followed the instructions. The release phase solution consisted of 0.02M phosphate buffer (pH 7.4)
00 ml, the rotation speed of the basket was 50 rpm, and the temperature was 37°C. The results are shown in Figure 1. As is clear from FIG. 1, the release of Na valproate from the suppository was suppressed depending on the amount added by adding Plantago Obata seed coat powder.

Experimental Example 2 Indomethacin release experiments from the suppositories obtained in Examples 8-10 and Comparative Example 2 were carried out in accordance with Experimental Example 1. The results are shown in FIG. As is clear from FIG. 2, the release of indomethacin from the suppository was suppressed depending on the amount of Plantago Obata seed coat powder added, and the effect was particularly significant when 10% or more was added.

Experimental Example 3 The suppositories obtained in Example 2 and Comparative Example 1 were administered rectally to domestic rabbits, and after administration, the plasma valproic acid concentration was measured over time. The results are shown in FIG. As is clear from FIG. 3, the rapid increase in plasma valproic acid concentration after administration of the suppository was suppressed, and furthermore, the plasma concentration was sustained.

Experimental Example 4 The suppositories obtained in Example 9 and Comparative Example 2 were administered rectally to domestic rabbits, and after administration, the plasma indomethacin concentration was measured over time. The results are shown in FIG. As is clear from FIG. 4, the rapid increase in plasma indomethacin concentration was suppressed, and furthermore, the plasma concentration was sustained.

[0029]

[Brief explanation of the drawing]

FIG. 1 shows the elution pattern of sodium valproate from suppositories.

[0030]

FIG. 2 shows the elution pattern of indomethacin from suppositories.

[0031]

FIG. 3 shows the relationship between the plasma concentration of valproic acid and the elapsed time when a suppository was administered into the rectum of domestic rabbits.

[0032]

FIG. 4 shows the relationship between the plasma concentration of indomethacin and the elapsed time when a suppository was administered into the rectum of a domestic rabbit.

Claims (5)

[Claims] 1. A sustained-release composition for vaginal or rectal administration, comprising a drug, a plantago plant-derived gum, and a base. 2. The composition according to claim 1, wherein the Plantago plant is Plantago obata. 3. The composition according to claim 1, wherein the gum is derived from the seed coat powder of Plantago lobata. 4. The composition according to claim 1, wherein the gummy content derived from the seed coat powder of Plantago lobata is 50% by weight or less. 5. The composition according to claim 1, which is in the form of a suppository or a rectal capsule.