JPS61176522A - Suppository for lubrication - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

TECHNICAL FIELD OF THE INVENTION This invention relates to a lubricant in the form of a suppository, particularly suitable for human cavities.

One of the features of this invention relates to a pre-coital lubricant in the form of a suppository, and another feature is that a solid suppository is inserted into the vagina to lubricate the cavity, and the suppository changes from solid to liquid in the body at body temperature. It turns into a lubricant, but it should be able to maintain a solid state of up to about 60% during transportation and storage. Yet another aspect of the invention relates to a method for making lubricating suppositories from a plurality of solid objects, at least in part consisting of components that are smooth at room temperature.

Various lubricants have been proposed. The requirements for such surface lubricants vary depending on the reason for lubricating the interior surface of the conduit. The human body naturally functions to produce lubricant before and during sexual intercourse. However, there is a need for materials that assist in the function of this natural lubricant.

In theory, any lubricant that is harmless to the skin could be used as a pre-coital lubricant - petroleum jelly, mineral oil, triglycerides, for example? Biologically inert lipophilic substances similar to oils and coke were used. but,
These substances have a flash point, such as staining the fibers), are not very compatible with intralayer moisture, and are difficult to remove from the skin or vaginal cavity when washed with fresh water. Efforts are being made in the pharmaceutical and other industries to develop a supplement suitable for pre-coital and other intravaginal lubrication. KY Jelly (trade name) is a general-purpose lubricant used when inserting thermometers and other instruments into the vagina or rectum during midwifery or gynecological procedures. %''0rthe Personal' Lubricant sold commercially is intended only for sexual intercourse.

However, its composition is somewhat similar to sterile general-purpose jelly.

Both products contain water as the main ingredient combined with cellulose derivatives and are packaged in collapsible tubes.

Since these products are water-based, they have many advantages over oil-based products, but conversely, the water-based portion contributes significantly to lubrication, so if it evaporates, the lubricating effect is lost. Such evaporation can even occur during sexual intercourse.

When it is necessary to insert an object into a cavity of the human body, especially the vagina or anus, suppositories have many advantages and are preferred by patients as well as doctors. Suppositories are highly developed as a matrix for drug release. Suppositories can also be lubricated as described in US Pat. No. 43.776.001. There is much literature regarding lubricants such as O which can render at least the surface of dosing devices, cotton balls, etc. lubricant, for example U.S. Pat.
00:3.884,233:3.886.940
: 4,026.292 : 4.140.756 :
4,347,237.

Suppositories generally produce a release or lubricating action of the drug from a solid to a liquid when placed in a body duct. Therefore, the melting point of the drug is about 30 to 37°C, that is, about the temperature of the human body.

It must be said that this level of melting point is relatively low compared to the temperature at which suppositories are transported and stored. For example, in Central and South America, the Mediterranean, Africa, and Southeast Asia, temperatures often reach 40 to 60°C, so such suppositories may become deformed, softened, or liquefied before use.

[Summary of the invention]

This invention was made in view of the above circumstances, and is suitable for forming into suppositories, exhibits lubricity independent of large amounts of moisture and humidity, and has better washability than conventional oil-based lubricants. The purpose is to provide a good pre-coital lubricant.

That is, the present invention provides a continuous phase containing an oxyalkylene I-lyol component containing (al) I-lyethylene glycol having a molecular weight of 200 to 20,000, the ethylene glycol component having a high degree of resistance to transportation in tropical regions. A substance that has a melting point but allows the suppository to liquefy in the human body: (b) 13 to 53 parts by weight (10 to 40 parts by weight of the suppository) of nonionic surfactant per 100 parts by weight of the above polyol component and (e) about 6 to 30% by weight (based on the suppository) based on the polyol component. A lubricant (generally ranging from 5 to 25 weight) which is uniformly dispersed in the continuous phase by the action of the nonionic surfactant; and a suppository comprising: It is.

The suppository of this invention is liquefied by inserting it into the vaginal cavity,
Provides lubrication before intercourse.

This liquefaction is generally completed within 2 to 30 minutes.

If desired, the suppository can be inserted up to several hours before intercourse.

The suppository of the present invention is made by heating polyethylene glycol slightly to dissolve it uniformly, dissolving the desired nonionic surfactant (or a combination of surfactants), and dispersing the lubricant in the heated mixture. Used as a medium for After the mixture is formed in a carrier, it is cast into the shape of a suppository by surrounding it with a mold or a suppository packaging material that functions as both molding and packaging.

The suppositories of the present invention are particularly suitable for pre-coital lubrication, but can also be used for inserting medical devices into body ducts. For pre-coital lubricants, water or moisture can be used not only for washing with water but also for liquefaction and uniform dispersion (in the vaginal cavity) of the suppository due to its compatibility with natural vaginal moisture. Compatibility with is desired. In addition, it is desirable for the lubricant to have a relatively low viscosity in the molten state in order to improve the pre-coital lubrication effect; such a low viscosity allows the lubricant to easily flow out of the vaginal cavity and into clothing. This is not desirable because there is a risk of In order to improve this drawback, the suppository of the present invention is designed to have extremely high compatibility with water, to improve the dispersion of the oily lubricant, and to combine nonionic surfactants and polymers. Since it has good compatibility with oxyethylene glycol paste, even if it leaks onto the cloth and stains it, it can be easily washed off with fresh water. The neutralized compositions of the present invention do not contain solids that will not be dispersed or suspended in water. Even conventional cellulosic materials are more difficult to disperse and suspend in water when compared to the compositions of the present invention. Dilioxyalkylene polyol component is f
It has excellent water solubility because it is composed of f&lyethylene glycol.

In addition, since the nonionic surfactant dissolves easily in ethylene glycol, the phase relationship between glycol and lubricant is simplified. The concentration of the nonionic surfactant is sufficiently large so that the lubricant is sufficiently emulsified, and even if spilled onto the fabric, the lubricant will be re-emulsified and will be protected.

Suppositories made of the composition of the present invention easily change from solid to liquid at human body temperature when inserted into the vaginal cavity. This phase change from solid to liquid in the body at body temperature can be called melting, as evidenced by experience, even though the melting point of the suppository itself during transportation or storage is 40 to 60°C.

When the suppository liquefies within the vaginal cavity, it mixes with natural moisture and rapidly disperses within the vagina. Furthermore, the lubricity is not lost even when moisture evaporates during sexual intercourse.

In addition to the glycol, lubricant, and surfactant composition of the present invention, a lower aliphatic hydrophilic polyol monomer soluble in the glycol may be added, and a preferred polyol monomer is glycerin. Pigments, fillers, extenders, preservatives, antioxidants, etc. may be added, but it is preferable not to use any of these that leave visible solid residues. various compounds approved by
For example, BHT (deltylated hydroxytoluene)
Alkylated hydroxyaromatic compounds such as , BUT (butylated and dioxyanizole) can be used.

One preferred example of the composition of the present invention will be described below.

Continuous Phase The main component of the continuous phase is polyoxyethylene or ethylene glycol alone or in combination. These glycols have extremely good compatibility with water <, 0.1~
Contains oxyethylene chains with hygroscopic properties of one or more widths of glycerin.

These polyethylene glycols cause most of the lubricating suppositories to become obsolete, and glycol C (or a combination thereof) is preferably kept at room temperature (20-25°C), and more preferably during transportation and storage in tropical regions. So it is necessary to keep it solid at that temperature. On the other hand, if the melting point of the glycol component is too high, i.e. above about 75°C, suppositories are usually
This means that it will not dissolve in the body, which is below 7 degrees Celsius. Therefore, the melting point of the glycol component is 75°C or lower, preferably 60°C or lower.
It is necessary to choose one that is below ℃. The melting point of this glycol component may be lowered by mixing a liquid or a solid with a low melting point with compatibilism.The low melting point solid or liquid for lowering the melting point has a molecular weight of 1.0.
00 or less (equivalent weight of 500 or less). Generally, commercially available low melting point glues have a molecular weight of about 200 or more.

Although polyoxyethylene glycol with a molecular weight of 1 or more is also available, in the case of the present invention, a polyoxyethylene glycol with a molecular weight of 20.0
Those above 00 have a relatively high melting point and are therefore not useful.
That is, the glycols useful in the present invention have an average molecular weight of about 400 to 14,000, and therefore a melting point of 75°C.
) Preferably, the temperature is 60°C or lower. Also, average molecular weight 7
,000-9,000 glycol with an average molecular weight of 300
It is good to mix with ~500 glycol in a ratio of 1:0.5~30.

In order to ensure water washability of the lubricant composition of the present invention, it is necessary to sufficiently disperse a surfactant having good compatibility with polyethylene glycol in the continuous phase, and furthermore, it is necessary to sufficiently disperse the surfactant which is compatible with polyethylene glycol in the continuous phase. For example, it is important to have a water solubility of 50% by weight or more. A characteristic of ethylene glycol is that it has water solubility even though it is a polymer with relatively large ethylene oxide. In the case of this relatively small molecular weight primer with a terminal hydroxyl group, water solubility decreases, but not so sharply, as the molecular weight that is completely or almost completely soluble in water increases to several thousand. 0 The polyoxyethylene glycol used in the present invention has a water solubility of 50% or more in terms of weight/weight (-su) either in the mold part or in combination.Therefore, the oxyethylene polymer is mixed with the oxyethylene polymer or tetramethylene oxytermer. Among nonionic polymers, it is difficult to improve the water solubility of oxyethylene (i.e., ethylene oxide) polymers, and the water compatibility of propylene oxide or other oxyalkylene polymers is undesirable. The oxyalkylene chains derived from two-carbon oxyalkylene units are unique in this type of structure, especially in terms of water compatibility. Unless modified with oxyethylene units, other hydrophilic solids, such as cellulose, cannot possess this remarkable water compatibility.

Relatively hydrophobic or lipophilic compounds that would impair the water compatibility of the glycol component of the invention are preferably excluded from the compositions of the invention. With the exception of extremely small amounts of antioxidants, preservatives, etc., the least hydrophilic component of the compositions of the present invention is the lubricant, which is substantially insoluble in submerged water.
.

Typically in the suppository compositions of the present invention, the glycol component accounts for 50-90% by weight, preferably 60-80% by weight. Furthermore, a nonionic surfactant is contained in the continuous phase in a uniformly dispersed (dissolved, diffused, or suspended) state. and surfactants (including mixtures) in an amount of 1.0 to 40% by weight of the total suppository, preferably 10 to 20% by weight.

In general, it is preferred that the surfactant component has good compatibility with the continuous phase, thereby simplifying the phase relationship in the composition; furthermore, the surfactant component should have good compatibility with water. preferable. This can be achieved by selecting an HLB value of 12 or more, preferably 14 or more. In addition, H
It is considered that an LB value of 8 or less is lipophilic, a value of 9 to 11 is intermediate, and a value of 12 or more is hydrophilic. Although surfactants with an HLB value of 20 or 30 or more are known, it is not necessary to use a nonionic surfactant with an HLB value of 18 or more.

When surfactants are used in combination (C, which is particularly preferred in this invention), the overall ML, B value is determined at the weight average pace commonly used in the detergent industry. Some nonionic emulsifiers and other surfactants are actually soluble in molten polyoxyethylene glycol. The most common of such surfactants are those containing oxyethylene chains.

For example, poly(oxyethylene) allester,
Poly(oxyethylene)teriol ether or a mixture of these esters and ethers. Some of these, such as polyoxyethylene (20) sorbitan monooleate, are also water soluble. Several types of polyoxyethylene ethers of higher aliphatic alcohols are commercially available. High-grade aliphatic Cal? 4-lyoxy-engineered tyrene derivatives of phosphoric acid, such as 9-lyoxyethylene deliol alkanoates, are also commercially available. Are unsaturated aliphatic carginic acids and alcohols also prescribed? It can be used to form lyoxyethylene derivatives. A considerable degree of higher aliphatic character can be produced using acids and alcohols having 6 or more carbon atoms, preferably 10 or more carbon atoms. If it is 028 or more, the aliphatic characteristics are excessive.]
, C20 or C22 is also slightly excessive. Relatively hydrophilic cores, such as sorbitan and other lower aliphatic I-liol monomers, balance the aliphatic nature of the carbon chain and can range from CI2 to C20. An example of a compound balanced in this way is polyoxyethylene (
20I) Sorbitan monooleate.

A preferred example of the surfactant mixture used in the present invention is one consisting of polyoxyethylene lauryl ether and 4-lyoxyethylene stearate. The weight averaged HLB of this mixture is about 14-18. Other preferred mixtures include polyoxyethylene lauryl ether having an HLB value of about 16.5 to 17 and optionally a HLB value of about 1.
5 polyoxyethylene sorbitan monoole), HL
n value of about 16.5-17? Contains lyoxyethylene stearate. These surfactants are used in proportions of 5 to 10% by weight, 0 to 5% by weight, and 0 to 10% by weight (all based on the entire suppository).

Distinct advantages are obtained by adding lower aliphatic hydrophilic polyol monomers to the continuous phase. For example, glycerin has a particularly good affinity for water and has a hygroscopicity that is about 10 to 100 times as strong as 't'lyoxyethylene glycol Q. Glycerin is in fact commonly incorporated as a wetting agent, solvent, plasticizer, and softening agent. Glycerin is also included as a common ingredient in suppositories and is considered to be safe and effective for medicinal use. The surfactant used in this invention is also safe and preferably in the i range. It is also approved for food or pharmaceutical use. Although glycerin is not essential in the suppository of the present invention, it is generally added in an amount of about 0 to 20% by weight, preferably 5 to 20% by weight based on the entire suppository.

Emulsified Phase The main and important component of the emulsified phase in the continuous phase is a lubricant (effective and safe for lubricating or plasticizing human skin). Examples of such lubricants include: are triglyceryl fatty acids (e.g. capric acid, cabrylic acid, lauric acid, myristic acid, lumitic acid, oleic acid, etc.); derivatives of fatty acids such as fatty acid esters (e.g. isozolol myristate, isopropyl/4 lumitate); fatty acids and fats Esters of group alcohols, such as lanolin; aliphatic fluols, 7'l-t, hacetyl alcohol, stearyl alcohol, oleyl alcohol; and mineral hydrocarbons, such as mineral oil, petroleum jelly, /4 rough-in wax, and the like.

A preferred example of the lubricant from the standpoint of economy, safety, and effectiveness is mineral oil.

Many suitable lubricants are insoluble or sparingly soluble in water. However, due to the presence of an effective emulsifier or surfactant, the suppository of the present invention has good water washability, and even if it adheres to cloth or textiles, it can be almost completely removed by washing with fresh water. Furthermore, this emulsifier system achieves uniform melting when the suppository is liquefied. In the suppositories of the present invention, the lubricant is very well dispersed, so that it approaches a true solution.

In typical compositions of the invention, the lubricant may represent 5 to 25% by weight, preferably 5 to 15% by weight (based on the total suppository).

Manufacturing method Since oxyethylene glycol is the main component of suppositories, it is first put into a heated mixer. The temperature in the mixer is such that the glycol remains molten, but does not reach the ignition point of any component of the composition. Generally, the temperature inside the mixer is 75
There is no need to raise the temperature above ℃. This is because most oxyethylene glycols dissolve at temperatures below 70°C. The above glue forms a transparent melt,
A nonionic surfactant is added to this. Preferably, in this case it is dissolved by stirring, the lubricant is also added under stirring and can be completely dispersed in 15-20 minutes. As a result, a material mixture is obtained, to which glycerin or other hydrophilic polyols etc. can be added at appropriate stages.

This heated mixture is poured from the mixer into the mold, released from the mold,
Each is then wrapped in foil/laminate packaging. It is also preferable to cool the mold to promote solidification of the molded product. Alternatively, the heated mixture may be poured directly into the preformed suppository packaging material, and the shaping and packaging may be carried out directly.

A preferred method of using the rice crackers of this invention is to insert the rice crackers into the vagina at least 5 minutes before sexual intercourse. If this method is inconvenient, it may be inserted 1 to 2 hours before intercourse, so that a sufficient amount of lubricant is maintained within the intercourse before intercourse begins. Even if the rice crackers completely melt and leak from the vaginal cavity, the effectiveness of the lubricant will maintain the effectiveness of the rice crackers due to their miscibility with the natural moisture within the vagina and their ability to spread within the vagina.

Example A suppository composition having the following composition was used for molding.

The HLB of polyoxyethylene lauryl ether and polyoxyethylene stearate is usually 16.5 to 1.
The range is 7. Therefore, the average HLB value of the nonionic surfactant system of this invention is about 16. This glycol component is kept in a molten state in the temperature range of 55-70°C.

The production was carried out in a batch manner, but it can also be carried out in a continuous manner.

For 10,000 parts of the above composition, BHT (antioxidant)
1 part was added. Rice crackers made from this composition are 30 meters long and 11 meters wide (the widest part). In addition,
Rice crackers with a length of 10 to 55 mm and a width of 2 to 2 mm can also be formed into containers.

Although fk- is generally preferred, drugs related to sexual intercourse, such as sperm inactivators, bactericidal agents, etc., can also be added to the suppository.

In this specification, the terms "polyethylene glycol and polyoxyethylene glycol" are used synonymously.

Claims (10)

[Claims] (1) (a) A continuous phase containing a water-soluble polyoxyalkylene polyol component comprising polyoxyethylene glycol having a molecular weight of 200 to 20,000 and accounting for 50 to 90% by weight of the entire suppository, wherein the polyol component is 75% by weight. ℃
(b) 10 to 40% by weight of a nonionic surfactant with an HLB value of 12 or more dispersed in the continuous phase (based on the entire suppository); (c) the continuous phase 5-25% by weight of lubricant dispersed in
(For the entire suppository); A lubricating suppository, characterized in that it becomes a homogeneous liquid in the human body but remains solid at temperatures of 40 to 60°C in the outside air. (2) The suppository according to claim 1, wherein the continuous phase further contains a dissolved lower aliphatic hydrophilic polyol monomer. (3) The suppository according to claim 2, wherein the hydrophilic polyol is glycerin. (4) Claim 1, wherein the surfactant component is composed of a mixture of oxyethylene chain-containing esters or ethers, has an HLB value of 14 or more, and the ester or ether functional group contains a higher aliphatic residue. Suppositories. (5) The suppository according to claim 4, which has an HLB value of 18 or less. (6) (a) Made of a mixture of polyoxyethylene glycol with a molecular weight of 400 to 14,000 and a melting point of 60°C
(b) 5 to 25% by weight of mineral oil dispersed in the above mixture; (c) a nonionic surfactant dispersed in the above mixture, comprising: , polyoxyethylene polyol ester, polyoxyethylene polyol ether, and mixtures thereof, with a weight average HLB value of 14 or more in an amount of 10 to 40% by weight; (d) glycerin 20 dispersed in the above mixture; weight%
1. A lubricating suppository comprising the following: Uniformly liquefied in the human body, but retaining a solid state at temperatures of 40 to 60°C under outside air. (7) The suppository according to claim 6, wherein the glycol mixture further contains an antioxidant. (8) The glycol mixture comprises: (a) polyoxyethylene glycol with an average molecular weight of 7,000 to 9,000; (b) polyoxyethylene glycol with an average molecular weight of 300 to 500; ) = 3:1 to 0.5:1, the amount of glycerin is 5 to 20% by weight, and the nonionic surfactant has a weight average HLB value of 14 to 18.
7. The suppository according to claim 6, which is made of a combination of polyoxyethylene lauryl ether and polyoxyethylene stearate and has a melting point of 45 to 60°C. (9) The above glycol mixture is 60-80% by weight, mineral oil is 5-15% by weight, glycerin is 5% by weight, HLB value 1
5 to 10% by weight of polyoxyethylene lauryl ether of 6.5 to 17, 5% by weight or less of polyoxyethylene sorbitan mono-oleate of HLB value of 15, HLB value of 16
．． 9. The suppository of claim 8, comprising 10% by weight or less of polyoxyethylene stearate of 5 to 17 and an effective amount of an alkylated hydroxyaromatic antioxidant. (10) (a) A step of uniformly melting the solid polyoxyethylene glycol mixture at a temperature of 75° C. or lower;
A step of dissolving ~53 parts by weight of a nonionic surfactant with an HLB value of 12 or more while keeping it in a liquid state at room temperature; (c) Adding 6 to 3 parts by weight of the above glycol to 100 parts by weight
A method for producing a lubricating suppository, comprising the steps of uniformly dispersing 0 parts by weight of a lubricant at room temperature or higher; and (d) casting and solidifying the same into a suppository.