JPS6078916A - Preparation of stable suspension for internal use - Google Patents

Abstract

PURPOSE:To obtain the titled suspension of hardly water-soluble or water-insoluble drug, having high physical, chemical and biological stability, by adding a nonionic surface active agent as a suspension assistant and if necessary a clouding point-raising agent such as edible saponin to a natural polysaccharide used as a suspension agent. CONSTITUTION:The objective stable suspension for internal use can be produced by adding a small amount of a nonionic surface active agent (e.g. polyoxyethylene sorbitan fatty acid ester, sorbitan fatty acid ester, etc.) having a clouding point of preferably >=75 deg.C to a natural polysaccharide (e.g. pectin, gum arabic, etc.) used as a suspension agent. If necessary, the effect of the surface active agent is improved by adding a clouding point-raising agent such as edible saponin, edible glycoside, propylene glycol, etc. The addition of the surface active agent gives a suspension agent preservable stably for a long period at a low temperature and sterilizable without losing the suspending property and acid resistance.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a pharmaceutical suspension for internal use that is physically and chemically as well as biologically stable.

Today, many pharmaceutical products are provided in the form of solid medicines such as tablets, pills, capsules, troches, buccal preparations, or suppositories for convenience in handling. However, all of these solid drugs act only after disintegration in the body followed by dissolution or elution, so there is a time lag of about 20 to 30 minutes before they take effect compared to liquid preparations. This is a well-known fact. On the other hand, solution preparations are absorbed immediately after administration, so their action may be too rapid. It is currently not possible to manufacture liquid formulations for internal use for certain groups of medicines; however, for some medicines it is preferable to administer them in powdered form rather than in tablet or capsule form. may be estimated to be safer or more effective.

For example, in the case of potassium chloride, when administered in the form of a tablet, it locally produces a solution with a high degree of C, which irritates the stomach wall and has been reported to cause gastric ulcers and gastric perforation in many cases. Furthermore, even with antisaponifiable gastric medicines and gastric mucosal protectants, it is preferable to administer them as a powder and diffuse them throughout the gastrointestinal mucosa, rather than administering them in the form of tablets. However, even in this case, it is of course necessary to drink a sufficient amount of water at the same time, and of course, a satisfactory effect cannot be obtained if only a small amount of water is drunk.

Above are two examples where it is desirable to administer medicines in powder form, but in these cases, a certain amount of water must coexist with the medicine, so that the appropriate amount of water must be taken when taking it orally. In terms of effectiveness, the use of aqueous solutions or suspensions of pharmaceuticals, especially the latter, is advantageous for this purpose.
It is also easy to imagine that it would be suitable from a safety standpoint.

This objective can be achieved by using pharmaceuticals that are insoluble or poorly soluble in water.

However, stably suspending a poorly soluble or insoluble drug in water is not so easy in practice, and may be extremely difficult depending on the type and physical properties of the drug. Especially when considering long-term storage, it is necessary to prevent contamination by mold and bacteria, but the use of preservatives is therefore undesirable from a safety standpoint, so heat sterilization methods are inevitably adopted. It turns out.

However, many suspension agents become less effective when the temperature exceeds 80° C., which is the minimum temperature required for sterilization, and their components tend to separate. This tendency is particularly noticeable when the reagent is a natural polysaccharide such as sodium alginate or gum arabic.
This tendency is particularly remarkable for acidic 11!1'. In addition, depending on the type of suspension agent, even if sheet metal heat sterilization is possible, it may gel non-thixotropically when simply cooled to room temperature or, to a lesser extent, when left in a cold place for a long time in winter. In many cases, it becomes unbearable to drink. Typical examples include pectin, carrageenan, and guar gum.

In this way, commonly used suspensions have many drawbacks in terms of heat resistance, acid resistance, gelling properties, etc., so in order to put suspension preparations for internal use into practical use, it is necessary to It is necessary to solve various problems.

However, as a result of conducting systematic research on many insoluble or poorly soluble pharmaceuticals, nutritional supplements, and foods, the present inventor found that this problem was solved in small amounts compared to natural polysaccharides as suspension agents. The effect of the above nonionic surfactant can be substantially solved by adding a small amount of propylene glycol or edible saponin or edible saponin-containing plant extract or We have discovered that the effect of edible glycosides or U (U) can be further enhanced by the addition of edible glycoside-containing plant extracts. That is, the suspension preparation for internal use obtained by the above method can be used in a sterile temperature environment. does not lose its suspending properties or acid resistance,
Moreover, it has the desirable property that there is no fear of gelation even if it is stored for a long period of time under cold conditions. The results of testing the effects of various suspending agents on a 5% aqueous suspension of magnesium hydroxide are shown below.

(Blank below) B: Surfactant + Probylene Glycol As shown by the above experimental results, the conventional use of a single suspension of 17-silicon suspension makes it difficult to stabilize water-insoluble pharmaceuticals against the effects of heat, etc. Although it is difficult to make it cloudy, adding a nonionic surfactant or even propylene glycol to it significantly improves the stability.

The present invention is based on the above knowledge, and its gist is that when suspending water-insoluble or poorly soluble pharmaceuticals in water using natural polysaccharides as a suspending agent, fJ, J% auxiliary agent If necessary, use 1 Jt of a non-ionic class IrI agent and, if necessary, an equinox depressant such as propylene glycol or erophagous saponin. Examples of the R+ ionic surfactant include polyoxyethylene sorbitan fatty acid ester, polyoxyethylene alkylphenyl ether, sorbitan fatty acid ester,
Examples include propylene glycol fatty acid ester, polyglycerol fatty acid ester, sugar ester, malic acid monoglyceride, etc., or those that are preferably 11f edible and whose equinox is 75°C or higher are classified as II.
It's frightening. These surfactant hIs are used within a range of 0.01 to 5% based on the total weight of the suspension formulation composition. j? J. As the clouding agent, propylene glycol, edible saponin or edible saponin-containing plant extract, edible glycoside, or edible glycoside-containing inoextract is used as the turbidity agent, but 111 of these auxiliaries - is 0.05-5% for the total 1.1 of the composition in the case of Maeba; When using an extract containing 11 molecules in the glycoside arrangement, its jlX is naturally 11, which corresponds to the saponin or glycoside it contains.) In addition, examples of the 11 IIf edible saponins include legume saponins (such as Thai saponin), heterin, cyframin, chrysiridine, clycyrrhizin,
Cioscin and Niskin'9 can be mentioned as examples, and plants containing these include, for example, Quillaja, carrot,
Examples include nuthu, chikaya, waremokou, chu, rakanka, nikaki, taisu, akebia, talanoki, and spinach.

The composition of the present invention may further contain additional ingredients such as sugar, flavor, fragrance, and color. The selection and amount of these auxiliary ingredients are determined from the viewpoint of ``pharmaceutical considerations and ease of administration.''

In principle, the pharmaceutical agent that serves as the starting agent for the composition of the present invention is poorly soluble or insoluble in water, but if necessary, it can be used by making it poorly soluble or insoluble. Means for this include, for example, coating with gastric or enteric film-forming materials, insoluble chlorination,
Known pharmaceutical means such as complexation, esterification, and inclusion are employed.

Hereinafter, we will give examples to briefly describe the manner in which the invention is carried out, but these are, of course, for illustrative purposes and do not intend to limit the spirit of the invention. isn't it. It should be understood that the drugs covered by the invention are not limited to the antacids and antidiarrheals mentioned above, but include all drugs that can be administered orally. .

Example 1 (Internal use 11j1 butyric suspension p: J preparation) Bikun Monooreko-i (trade name: Poritsuruhe-180) 0.05g gum arabic powder 15g propylene glycol 4g ginseng extract (1:10) 0.3g Add purified ice and make: I'5 90 ml [Power: 1 person] Pour about 30ml of purified water into a homomixer, stir, then add gum arabic powder and macanesium aluminum silicate and stir to make a homogeneous suspension.

Separately, cinnamon oil, boriogyshiethylenesolhytan oleate I, and propylene glycol were stirred and combined and added to the above suspension, and then about 2 f) ml of purified ginseng extract and white sugar were added. After adding and mixing the melted solution to the ice cubes, the whole mixture is transferred to a homogenizer and homogenized for about 5 minutes. Once the homogenization is complete, add purified water to bring the total volume to 90 ml, stir well, and then dispense 30 layers one by one into small glass bottles. This bottled product is first heated at 100° C. for 30 minutes, then after 24 hours, heated and sterilized again under the same conditions to form a sterile suspension preparation.

This product is a long-term stable sterile suspension formulation,
Even if it is made in cold temperatures, it can be taken internally for the purpose of suppressing milk without fear of solidification. The standard dose is three times a day, one vial at a time.

Example 2 (positive suspension preparation for internal use) [Prescription] Medicinal charcoal 1.5g Urundesoxycor-Rum O, 02g Unlubitol liquid (85%) 8.0ml 1 sentence - Menthol 0.02g Polyoxyethylene sorbitan Monooleate
0.05 g gati gum 0.08 g Add purified water to make a total volume of 30 ml Add menthol, polyoxyethylene, and
After adding sorbitan monooleate and propylene glycol and stirring to dissolve them in advance, purified water 151, Gatica, and other remaining components are added, stirred again, mixed, and homogenized using a homogenizer. Next, further purified water was added to bring the total volume to 30 ml, and the mixture was filled into a glass bottle.Tyndall sterilization was carried out in the same manner as in the previous example.The product obtained was a stable black color (717 suspension formulation,
Take 30111 (J&;human) at a time to prevent diarrhea (1 dose).

Special 31 applicant: Tanpei Pharmaceutical Co., Ltd.

Procedural amendment filed in February 1980, Patent Application No. 185679, 2, Name of the invention: Process for producing stable suspension for internal use, 3, Person making the amendment: Relationship with 11 yen Patent applicant address: Osaka Name: Tanpei Pharmaceutical Co., Ltd. Representative: Teruhiko Mori 4, Agent address: 1-32-125 Higashi Mikuni, Yodoyo-ku, Osaka City, Nikkan 1980-1 of the amended order March 31st (shipment date) 6. Number of inventions increased by amendment 0 7. Subject of amendment Illllll complete text 8 content Engraving of specification (no change in content) 9.
List of attached documents (1) IJF details (engraving method) 1 copy procedure -? M
lj orthodox book (II parrot.

Day 2, Name of the invention: Method for producing a stable suspension for internal use 1 3. Name to be amended 13 (Relationship with the matter) Address of patent applicant: Osaka Ha1, Ibaraki City, Ibaraki City, IJ71fi6, Name: Tanpei Pharmaceutical Co., Ltd. Co., Ltd. □Representative Mori To1; Hiko4, Agent Address 1-32-12 Higashi Mikuni, Yodoyo-ku, Osaka City, Number of inventions increased by amendment 0.

[2] Page 8 of the specification, 5th line from the bottom; Where it says [can be done and also includes these] [earth 2 dots are 1 stop, and nimu h ball is also included 1.1 - admonition Δ−

Claims (1)

[Scope of Claims] ] 1] A poorly water-soluble or non-water-soluble product characterized by containing a nonionic surfactant and, if necessary, a harmless equinox elevating agent in addition to a natural high-molecular polysaccharide as a suspending agent. Stable internal suspensions of insoluble pharmaceuticals. [2] The suspension for internal use according to claim 1, wherein the nonionic surfactant has an equinox point of 75°C or higher. (3) The equinox elevating agent is propylene glycol or U) edible saponin or an edible saponin-containing plant extract, or edible glycosides or edible glycoside-containing plant extracts. Suspension for internal use according to item 2. 141. The suspension for internal use according to any one of claims 1 to 3, wherein the suspension is heat sterilized.