JPH08151328A - Lubricating agent for preventing infection of aids - Google Patents

Abstract

PURPOSE: To obtain an AIDS infection-preventing lubricating agent useful for preventing the infection of the AIDS only by applying the lubricating agent on a vagina and having an effect also for smoothly performing the coitus of aged people, etc. CONSTITUTION: The AIDS infection-preventing lubricating agent contains a substance having an anti-AIDS virus action, preferably an acidic polysaccharide, especially carageenan. The lubricating agent includes the agent comprising 0.1-2wt.% of the acidic polysaccharide, 0-60wt.% of a polyhydric alcohol as a lubricating base material, 0.1-0.5wt.% of a water-soluble polymer as a lubricating effect-accelerating agent, 0.01-0.1wt.% of an antiseptic, and purified water, and having a viscosity of 5-300 centistokes. The water-soluble polymer is usually sodium alginate which may partially or wholly be replaced with hyaluronic acid or its alkali metal salt. It is estimated that the anti-AIDS action of the acidic polysaccharide is exhibited on the basis of its virus adsorption-inhibiting action.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to an AIDS infection preventing lubricant. It is an object of the present invention to prevent infection of AIDS by applying it to the vagina and the like, and also to prevent pain and the like so that sexual intercourse can be smoothly performed in the elderly.

[0002]

2. Description of the Related Art Conventionally, among patients who come to an obstetrics and gynecology department,
A woman who had postmenopausal or uterine removal surgery complained of pain during intercourse. This is probably because the genitals, which have been supported by female hormones, are atrophied with the decrease of hormones and the production of secretions is decreased. Lubricants are used in Europe and the United States to alleviate the pain during sexual intercourse. In Japan, the lubricant applied to the vagina etc. is also targeted for elderly people, and the product name is "Maloney Jelly, Fuji Latex Co., Ltd.", "Lube Jelly, Japan Family Planning Association" or "EX Jelly, Ryukakusan". It is sold at.

[0003]

[Problems to be Solved by the Invention] On the other hand, the spread of AIDS infection has become a very serious problem internationally, particularly in Asian and African countries. In recent years, the number of infected people has increased rapidly in Japan, and heterosexuality has passed homosexuality and become the main infection route (Aids equality laws and regulations notice collection-1992 edition, supervised by: Ministry of Health, Labor and Welfare, Tuberculosis,
Infectious disease control room. Issuance: AIDS Prevention Foundation) The situation of infection is approaching a new phase. Under such circumstances, a lubricant having an anti-AIDS effect was invented. That is, the root of the idea is that the application use is different from the oral administration, and the evaluation of the in vitro test is considered to be related to the clinical application. An object of the present invention is to provide a lubricant having an AIDS infection defense function.

[0004]

That is, the present invention is an AIDS infection preventing lubricant containing a substance having an anti-AIDS virus action. For conventional lubricants, polyhydric alcohols such as propylene glycol and glycerin are used as a lubricant base, and an antiseptic agent, a lubrication effect promoter, and water are mixed into the lubricant base.
A water-soluble, tasteless, odorless and highly transparent gel substance having a viscosity of 6.5 to 7.0 and a viscosity of 35,000 cps (BH type viscometer, No. 4 rotor 4 rpm) was used. The present invention is intended to contain an acidic polysaccharide having an anti-AIDS virus effect.

Acidic polysaccharides having an anti-AIDS virus activity in the present invention include those obtained from seaweeds, prokaryotes, nucleolibacteria, basidiomycetes or dicotyledons, or chondroitin sulfate, carrageenan, heparin, dermatan sulfate, keratan sulfate. Sulfated Schizophyllan, sulfated Gardlan, sulfated alkyl oligosaccharides, sulfated gangliosides, heparan sulfate or salts thereof are used.
These anti-AIDS virus actions may be anti-AIDS virus actions or anti-retrovirus actions. (In the present invention, such a substance is referred to as a substance having an anti-AIDS virus action).

The acidic polysaccharide having anti-AIDS virus activity used in the present invention may be obtained from any seaweed. For example, in brown algae, Shiomidori eyes, Kurogari eyes, Whip eyes, Amijiku eyes, Nagamatsu eyes, Key eyes, Urushigu eyes, Haha moth eyes, Ume moth eyes, It is an acidic polysaccharide obtained from Konbume, Hibamatama, etc. (see Japanese Patent Laid-Open No. 63-316731). In addition, in red algae, Chirinori eyes, Benido green eyes,
There are acidic polysaccharides obtained from the unseasoned eyes, the delicious eyes, the sea urchin eyes, the astringent eyes, the hide-and-sight eyes, the seaweed eyes, the dull eyes, the goose eyes, etc. (JP-A-63-3167).
32 gazette). Furthermore, in green algae, whiskers, eyes, black eyes, cracked eyes, blue eyes,
There are acidic polysaccharides that can be obtained from Kawame eyes, Yoyodorome eyes, Shiogusa eyes, Green eyes, Saya Midori eyes, Kasori eyes, Midori eyes, Eye eyes, etc. (JP-A-63-316733). (See the official gazette).

The acidic polysaccharide in the present invention is obtained by drying and crushing these seaweeds and extracting with cold water, hot water, alkaline aqueous solution, hot alkaline aqueous solution or hydrophilic organic solvent (methanol, ethanol, isopropyl alcohol, etc.). The extract is concentrated or salted out, dialyzed, ultrafiltered, reverse osmosis treated, gel filtered, precipitated by an organic solvent to remove low molecular weight compounds and purified, and in some cases further ion exchange is performed. It can be obtained by removing impurities by spray-drying, freeze-drying or the like. The extract may be concentrated and used as it is, or may be spray-dried, freeze-dried or the like before use. The α-naphthol sulfate reaction, indole sulfate reaction, acisulon sulfate reaction, phenol sulfate reaction, Lowry-Folin method, ninhydrin reaction after hydrolysis with hydrochloric acid, etc. are shown as positive or slightly positive. Further, the average molecular weight is 10 ³ to 10 ⁶ dalton by gel filtration chromatography. Whether or not these acidic polysaccharides have an anti-AIDS virus action is tested according to the method described in the test example below, and those having an anti-AIDS virus action (antiretrovirus action or anti-AIDS virus action) are used. .

The acidic polysaccharide used in the present invention can also be produced from prokaryotic fungi. For example, it can be produced from bacteria belonging to prokaryotic fungi, myxobacteria, actinomycetes, etc. (JP-A-63-316726). For these bacteria, Enterococcus faecalis, as described in the publication,
(IMA-1262), Pseudomonas aeurginosa (IAM-1514), B
ifidobacterium imfantis (ATCC 15697), Lactobacill
Cultured cells such as us casei ( IAM-1118) are used, and the acidic polysaccharide is collected in the same manner as described above.

[0009] Similarly, acidic polysaccharides obtained from Mycobacterium tuberculosis fungi such as Mycobacterium leprae, slime mold, oomycete, mold, zygomycete, ascomycete and imperfect bacterium can also be used (JP-A-63). -3
16735 and JP-A-63-316735). Examples of such Mycobacterium tuberculosis include Aspergillus glaucus ( IA
M 3005), Saccharomyces cerevisiae (IAM-42077),
Cultured cells such as Mucor spinescens (IAM-6071) are used. The acidic polysaccharide can be collected in the same manner as described above.

The acidic polysaccharide is obtained from a culture of a basidiomycete, particularly a basidiomycete belonging to the genus Astragalus, for example, CM 101 strain (Ministry of Engineering Research Accession No. P NO.2412), CM102.
The strain may be a strain (the same P NO.2413, CM 103 strain (the same P NO.2414) or a crestin (trade name) purified from these strains (JP-A-63-316734, JP-A-63-316734). JP-A-63-366726, JP-A-1-199593), and further dicotyledons (seeds such as gorse, Aedes japonicum, defatted soybeans, ground beans, lentils, etc.) (JP-A-63-316730) See) can be used.The extraction of acidic polysaccharides from these natural products can be performed by the same method as described above.
It is also possible to use chondroitin sulfate, carrageenan, heparin, dermatan sulfate, keratan sulfate, sulfated schizophyllan, sulfated guardlan, sulfated alkyl oligosaccharide, sulfated ganglioside, heparan sulfate, or medically acceptable salts such as sodium salt. .

However, among these acidic polysaccharides,
Using the carrageenan, a polysaccharide contained in the red alga Chordrus, Glgartina, Euchema,
It is most desirable from the viewpoints of AIDS infection prevention effect and feeling of use. As described above, the lubricant is an aqueous solution having a viscosity of 5 cst to 600 cSt, which is obtained by mixing a lubricating base material such as glycerin, propylene glycol, diethylene alcohol, and polyglycol with a preservative, a lubricating effect promoter, purified water, and the like. It can be obtained as a viscous liquid having a lubricating property. As the preservative, methylparaben, propylparaben and the like are used. Further, a water-soluble polymer is used as the lubricant effect promoter. Sodium alginate is usually used as the water-soluble polymer, but part or all of it may be replaced with hyaluronic acid or its alkali metal salt. Moreover, you may add a fragrance | flavor and a coloring agent as needed.

The amount of the substance having an AIDS antiviral effect used in the present invention is preferably 0.1 to 2% per 100 g of the lubricant. Also, polyhydric alcohol is 40
~ 60% by weight, lubricant effect promoter 0.1-0.5% by weight, preservative
0.01-0.1% by weight and purified water are used. They are,
An appropriate amount is mixed so that a viscous liquid having the above-mentioned viscosity and lubricity can be obtained within the above-mentioned use amount range. By applying the obtained viscous liquid to the genitals such as the vagina at the time of sexual intercourse, it can be useful for preventing AIDS infection, smooth sexual intercourse, and alleviate the pain associated therewith.

The anti-AIDS activity of the substance having anti-AIDS virus activity of the present invention is as follows. (Anti-AIDS action) 100 g of dried product of Hijiki (browns, Hibaramame, Honodaraceae, Hijiki genus) is shredded into a volume of 3
The mixture was placed in a stainless steel tank of L, 2 L of water was added, and the temperature was maintained at 90 to 95 ° C while stirring. After extracting for about 3 hours,
Cooled to room temperature. The extraction slurry was separated into an extract and a residue by a centrifugal separator. Extraction liquid is
It was concentrated to 400 ml and dried by freeze-drying to obtain about 20 g of acidic polysaccharide (KM-101). This may be used as it is, or further purified by ion exchange chromatography such as diethylaminoethyl cellulose to obtain an adsorbed substance having a concentration of 0.5 M to
Elution with a salt such as 2M NaCl or 0.1N NaOH or alkali gave a strong antiviral effect. A 10 mg / ml aqueous solution of the acid polysaccharide (KM-101) derived from Hijiki was prepared, and a diluted solution was prepared so that the final concentrations were 5000, 1000, 900, 40, 8, 1.6 and 0.32 μg / ml. HIV virus (HTLV-IIIB)
1 × 10 ^5.75 TCID50 / ml solution was prepared. 1 ml of MT-4 (CD4 positive human T cell line) cells susceptible to HIV infection was added to each well of a 24-well plate coaster at a concentration of 2 × 10 ⁵ / ml, and the diluted acidic polysaccharide solution and the HIV virus solution were added. Are mixed in equal amounts for 5 minutes, then 10 μl of the mixed solution is added to each well and incubated at 37 ° C in a carbon dioxide incubator.
On the 6th day, the number of HIV-infected cells was counted by an immunofluorescence method using an anti-HIV antibody, and the infection inhibition rate was calculated by comparing with the one using a solution containing no acidic polysaccharide.

KM-101 μg / ml HIV antigen positive cells (%) Inhibition rate (%) 0 61 ── 1.6 43 30 8 41 33 40 6 92 200 2 97 1000 0 100

(Antiviral activity, anti-AIDS activity) 1 unit of AMV reverse transcriptase (50 mM) in a reaction mixture (50 mM Tris-HCl, pH 8.4, 2 mH dithiothreitol, 100 mM KCl, 10)
mM MgCl ₂ , 0.1% Triton × -100, 50 μg poly (rA)-
Various sulfated polysaccharides were mixed in oligo (dT) / ml, 1.25 μCi [ ³ H] dTTP (57Ci / mmol)) at various concentrations. The reaction mixture was incubated at 37 ° C. for 30 minutes, the reaction was terminated by adding 5% trichloroacetic acid, the precipitate was collected with a glass fiber filter, and the radioactivity was measured with a liquid synchronization counter. The following results were obtained by defining 1 inhibition unit as the activity that inhibits 50% of 1 unit of reverse transcriptase activity.

[0016]

A sample of HIV reverse transcriptase was added to 0.5 ml of MOLT-
HIV reverse transcriptase HTLV-IIIB activity was measured by the same method as above, obtained from the supernatant of 4 / HIV cultured cells, and showed the same tendency.

Among the substances having an anti-AIDS virus action used in the present invention, acidic polysaccharides such as sulfated polysaccharides exhibit the above-mentioned infection inhibitory effect, and this action is exerted based on the virus adsorption inhibitory effect. It is considered to be one. The lubricant of the present invention has no side effect and can effectively exhibit the anti-AIDS virus effect with a high probability.

Next, the present invention will be specifically described with reference to examples.

[Example 1] Hijiki-derived acidic polysaccharide (KM-101) 0.30% by weight propylene glycol 10.30% by weight glycerin 39.70% by weight methylparaben 0.03% by weight propylparaben 0.01% by weight sodium alginate 0.20% by weight purified water 49.46% by weight

A composition having the above mixing ratio is mixed to obtain a viscosity of 5
An aqueous viscous liquid with high lubricity was obtained at ~ 600 cst. This was used as a lubricant.

[0021]

Example 2 Carrageenan 0.5% by weight Propylene glycol 9.0% by weight Glycerin 15.0% by weight Macrogol 400 14.0% by weight Sodium hyaluronate 20.0% by weight Methylparaben 0.2% by weight Fragrance 0.05% by weight Purified water 41.25% by weight

A composition having the above blending ratio is mixed to obtain a viscosity of 5 to 5.
At 600 cst, an aqueous viscous liquid with high lubricity was obtained. This was used as a lubricant.

[0023]

[Effects of the Invention] The lubricant of the present invention is effective not only for preventing the infection of AIDS but also for facilitating sexual intercourse for the elderly by just applying it to the vagina and the like.

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[Procedure amendment]

[Submission date] February 13, 1995

[Procedure Amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0011

[Correction method] Change

[Correction content]

However, among these acidic polysaccharides,
Red alga Chordrus, Glgartina, Euc
a polysaccharide contained in hema genus tying Na emission (Ca
It is most desirable to use rrageenan) from the viewpoint of the AIDS infection prevention effect and the feeling of use. As described above, the lubricant is a water-based solution having a pH of approximately 5 cst to 600 cSt by mixing a lubricating base material such as glycerin, propylene glycol, diethylene alcohol, and polyglycol with a preservative, a lubricant effect promoter, purified water, and the like. It can be obtained as a viscous liquid having a lubricating property. Preservatives include
Methylparaben, propylparaben and the like are used. Further, a water-soluble polymer is used as the lubricant effect promoter. Sodium alginate is usually used as the water-soluble polymer, but part or all of it may be replaced with hyaluronic acid or its alkali metal salt. Moreover, you may add a fragrance | flavor and a coloring agent as needed.

[Procedure Amendment 2]

[Document name to be amended] Statement

[Name of item to be corrected] 0015

[Correction method] Change

[Correction content]

(Antiviral activity, anti-AIDS activity) 1 unit of AMV reverse transcriptase (50 μl) in a reaction mixture (50 mM)
Tris-HCl, pH 8.4, 2mH dithiothreitol,
100 mM KCl, 10 mM MgCl ₂ , 0.1%
Triton × -100, 50 μg poly (rA) -oligo (dT) / ml, 1.25 μCi [ ³ H] dTTP (5
7 Ci / mmol)) and various sulfated polysaccharides were mixed at various concentrations. The reaction mixture was incubated at 37 ° C. for 30 minutes, the reaction was terminated by adding 5% trichloroacetic acid, the precipitate was collected by a glass fiber filter, and the radioactivity was measured as a liquid.
It measured with the scintillation counter. The following results were obtained by defining 1 inhibition unit as the activity that inhibits 50% of 1 unit of reverse transcriptase activity.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Naoki Yamamoto 3-11-17-501 Ebisu Minami, Shibuya-ku, Tokyo

Claims (5)

[Claims] 1. A lubricant for preventing AIDS infection, which contains a substance having an anti-AIDS virus action. 2. The lubricant according to claim 1, wherein the substance having an anti-AIDS virus action is an acidic polysaccharide. 3. Acidic polysaccharides, polyhydric alcohols, preservatives,
Viscosity consisting of water-soluble polymer is 5-3000 centistokes
AIDS infection control lubricant adjusted to (cSt). 4. The acidic polysaccharide is carrageenan.
Or the lubricant according to 3. 5. The lubricant according to claim 3, wherein part or all of the water-soluble polymer is replaced with hyaluronic acid or its alkali metal salt.