Mixture of sodium chloride and sugar in the manufacture of a medicament employed for treating lax vagina syndrome or colpoxerosis disease in a mammal

Abstract

The use of the mixture of a salt and sugar in the manufacture of a medicament employed for treating lax vagina syndrome or colpoxerosis disease in a mammal. Various tests, vaginal smooth muscle contractility test using New Zealand White Rabbit; (Experimental example 1); the effect on the vagina contractility in volunteers by using perinometer (Experimental example 2); and the effect on the colpoxerosis disease in volunteers (Experimental example 3), showed improving effect on the contractility of vagina tissue and colpoxerosis disease. Accordingly, the combination can be useful in treating or preventing lax vagina syndrome or colpoxerosis disease.

Claims

1. A method of treating lax vagina syndrome or colpoxerosis disease in a mammal, comprising the steps of: administering into a vagina of a mammal in need of treatment for lax vagina syndrome or colpoxerosis disease an effective amount of a combination consisting of: salt, comprising sodium chloride, selected from the group consisting of refined salt and un-refined salt, and a mono-saccharide selected from the group consisting of glucose, fructose, mannose, and galactose; together with a pharmaceutically acceptable carrier thereof, wherein the sodium chloride and the mono-saccharide comprise 20% to 99.99% by weight of the composition and wherein the weight ratio of the sodium chloride and the mono-saccharide is 1:1 to 1:10.

2. The method of claim 1, wherein the combination is contained in a composition selected from the group consisting of cleansing liquid, gel, jelly, foam, cream, ointment, lotion, balm, patch, paste, spray solution, aerosol, vaginal tablet, vaginal capsule, vaginal film, vaginal sponge, tampon, and pad.

3. The method of claim 2, wherein the composition is a cleansing liquid.

4. The method of claim 2, wherein the composition is a vaginal tablet.

Description

DESCRIPTION OF DRAWINGS

(1) FIG. 1 shows the comparisons of each resting tension between ring type and strip type vaginal tissue;

(2) FIG. 2 shows the intensity of contractility in response to the addition of K+ Krebs in ring type and strip type vaginal tissue.

(3) FIG. 3 shows the intensity of contractility according to the dose of test samples.

BEST MODE FOR CARRYING OUT THE INVENTION

(4) It will be apparent to those skilled in the art that various modifications and variations can be made in the compositions, use and preparations of the present invention without departing from the spirit or scope of the invention.

(5) The present invention is more specifically explained by the following examples. However, it should be understood that the present invention is not limited to these examples in any manner.

EXAMPLES

(6) The following Reference Example, Examples and Experimental Examples are intended to further illustrate the present invention without limiting its scope.

Example 1

Preparation of an Inventive Combination

(7) 1-1. Preparation of Processed Salt

(8) 900 mg of sea salt (Shinan, Korea, www.nhshinansalt.com) was melted for 24 hours at 850-1000° C. using by heater (MS-E104, TOPS Co. Ltd.) to obtain 400 mg of the processed salt.

(9) 1-2. Preparation of Refined Salt

(10) 400 mg of refined salt (NaCl, F.W. 58.44) was procured from the conventionally available company (SPPO-91701, Duksan company, www.duksan.co.kr).

(11) 1-3. Preparation of Glucose

(12) 800 mg of glucose (crystalline glucose) was procured from the conventionally available company (Samyang Genex Corp., www.genex.co.kr).

(13) 1-4. Preparation of Combination (1)

(14) 400 mg of the processed salt and 800 mg of glucose prepared in the above steps, were thoroughly mixed together to obtain 1200 mg of the inventive combination (designated as “SG1” hereinafter).

(15) 1-5. Preparation of Combination (2)

(16) 400 mg of the refined salt and 800 mg of glucose prepared in the above steps, were thoroughly mixed together to obtain 1200 mg of the inventive combination (designated as “SG4” hereinafter).

(17) The combinations were kept at −75° C. in refrigerator and used in following experiments by dissolving in distilled water before use.

Example 2

Preparation of Inventive Vaginal Tablet Composition (SG2)

(18) The combination prepared in Example 1 comprising 400 mg of processed salt and 800 mg of glucose was mixed with 2 mg of magnesium stearate in order to formulating into inventive vaginal tablet composition combination (designated as “SG2” hereinafter) using by entableting apparatus (KT2000, Kumsungkigong).

Example 3

Preparation of Inventive Vaginal Tablet Composition (SG5)

(19) The combination prepared in Example 1 comprising 400 mg of refined salt and 800 mg of glucose was mixed with 2 mg of magnesium stearate in order to formulating into inventive vaginal tablet composition combination (designated as “SG5” hereinafter) using by entableting apparatus (KT2000, Kumsungkigong).

Example 4

Preparation of Inventive Vaginal Cleansing Solution Composition

(20) The vaginal cleansing solution composition comprising the combination prepared in Example 1 (SG4) comprising 400 mg of refined salt and 800 mg of glucose was prepared by mixing together with following ingredients as shown in Table 1 (designated as “SG3” hereinafter) for 48 hours with stirring.

(21) TABLE-US-00001 TABLE 1 SG3 solution (100 ml) Ingredient Amount SG4 0.5 g Lactic acid 1 g adjuvant Whey 180 mg Ethanol 1 g Preservatives (benzalkonimum HCl and Trace amount menthol) Distilled water Appropriate amount to adjusted to 100 ml

Experimental Example 1

Vaginal Smooth Muscle Contractility Test

(22) To test the effect of inventive combination (SG3) prepared in Example on the vaginal smooth muscle contractility in New Zealand white rabbit, was performed by using organ bath according to the procedure disclosed in the literature (S-J Oh, et al., (2003), Histological and functional aspects of different regions of the rabbit vagina, International Journal of impotence research, 15, pp 142-150; N. N. Kim et al., (2004), Effects of ovariectomy and steroid hormones on vaginal smooth muscle contractility, International Journal of Impotence Research, 16, pp 43-50; A. Giraldi et al., (2001), Joint Award Winning Paper D Jean Francois Ginestie Prize Effects of diabetes on neurotransmission in rat vaginal smooth muscle, International Journal of impotence Research, 13, pp 58-66).

(23) 1-1. Preliminary Test

(24) Prior to principal test, a preliminary test in order to determining the type of test was performed after delivering rabbit vagina in consideration with the previous literatures.

(25) Through the preliminary test, it has been confirmed that the vaginal smooth muscle contractility in response to the addition of K+ (80 mM)-Krebs solution in the form of strip type rabbit vagina, showed stronger than that in the form of ring type rabbit vagina and moreover, the vaginal smooth muscle contractility according to the increased volume of phenylephrine in the form of strip type rabbit vagina, also showed stronger than that in the form of ring type rabbit vagina.

(26) At the result, it has been confirmed that the strip type rabbit vagina is more suitable to test the experiment rather than ring type rabbit vagina.

(27) 1-2. Experimental Animal

(28) 10 rabbits (New Zealand White Rabbit, Saeron Bio Inc., Korea, about 2.5-3.0 kg, 1 week aged) had been acclimated with the environment for 3 days with checking their health condition and used in the experiment.

(29) All the rabbits were marked with red oil-based pen during the acclimation period (to left ear auricle) and with black oil-based pen during test period (to right ear auricle). The breeding cages were marked with individual identification cards recording test number, test subject, test period and animal number etc.

(30) The testing animal had been bred and test was performed in the animal breeding room of KAMSI (Korea Animal Medical Science Institute, Korea) under the condition maintaining the temperature (23±3° C.), relative humidity (55±15%), ventilation number (10-20 times/hr), light cycle (light on at 08:00 and light off at 20:00) and illumination intensity (150-300 Lux). The breeding condition was constantly and periodically checked. The animal had been freely accessible to feed (KSN140203, Cargill Adri Purina Inc., Korea) and sterilized water. The animals had been bred in stainless steel breeding box (W 405×L 605×H 365 mm) at 1 rabbit per cage during acclimation, quarantine, administration and observation period.

(31) 1-3. Sample Treatment (Organ Bath Method)

(32) The inventive composition was administrated into the rabbit vaginal tissue according to the organ bath method disclosed in the literature as follows:

(33) The strip (1.5 mm×10 mm) of rabbit vagina surrounded with muscle of which mucose membrane had been removed, was dipped into Krebs solution (119 mM NaCl, 4.7 mM KCl, 1.1 mM MgSO.sub.4, 1.2 mM KH.sub.2PO4, 1.5 mM CaCl.sub.2, 25 mM NaHCO.sub.3, 10 mM D-glucose, G1009, Biosesang Corp. Korea) saturated with mixture gas (95% O.sub.2 and 5% CO.sub.2 gas) at 37° C. The end of trip was fixed and the other end was connected to transducer (model FT03; Grass instruments, Quincy, Mass., USA) to record the isometric tension of the strip with grass physiograph (AD instruments, USA) in 20 mL of chamber (FT03, GRASS Technologies).

(34) 1-4. Procedure

(35) Through various preliminary test with different conditions, following procedure was established. After stabilizing the strip of rabbit vagina with resting tension of 1.2 g for 30-60 mins in Krebs solution, the strip was contracted twice for 15 mins in K+ Krebs solution (43.7 mM NaCl, 80 mM KCl, 11 mM MgSO.sub.4, 1.2 mM KH.sub.2PO4, 1.5 mM CaCl.sub.2, 18 mM NaHCO.sub.3, 10 mM D-glucose, Biosesang Corp. Korea), washed with the solution three times to be stabilized and the comparative test for determining its contractility was performed.

(36) The intensity of vagina contractility was determined by comparing the contractility caused by K+ Krebs solution per tissue weight and the intensity of vagina contractility in a dose dependent manner was expressed by setting each intensity of K+ contractility to 100%.

(37) 1-5. Determination of Resting Tension

(38) Two kinds of rabbit vagina, i.e., ring type (3 mm) and strip type (1.5 mm×10 mm) were prepared and the resting tension of the vagina was chosen where the vagina was most stable and the contractility response against the addition of K+ Krebs solution after the stabilization had shown most apparently.

(39) As can be seen in FIG. 1 and Table 2, the contractility of ring type was 0.51 g in K+ Krebs solution when its resting tension was set to 2.0 g whereas it was increased to 0.54 g when its resting tension was set to 1.5 g. Accordingly, the testing tension of ring type was determined to 1.5 g considering the above test result and the stability of vagina tissue.

(40) The contractility of strip type was 0.31 g in K+ Krebs solution and severe convulsion happened when its resting tension was set to 2.0 g whereas it was increased to 0.42 g when its resting tension was set to 1.2 g. Accordingly, the testing tension of strip type was determined to 1.2 g considering the above test result and the stability of vagina tissue.

(41) TABLE-US-00002 TABLE 2 Resting tension in ring type and strip type vagina tissue Ring type strip type (tension unit: g) (tension unit: g) Resting tension 1.97 2.12 K+ Krebs 2.48 2.43 Tension difference 0.51 0.31 Resting tension 1.52 1.24 K+ Krebs 2.06 1.66 Tension difference 0.54 0.42
1-6. Test Result

(42) At the result, it has been confirmed that the strip type vagina tissue was chosen to use in the experiment since it showed the stronger contractility response against K+ (80 mM)-Krebs than the strip type vagina tissue (See FIG. 2).

(43) It has been confirmed that the contractility intensity in the test group treated with inventive composition (30-300 mg/ml) has been increased in a dose dependent manner compared with control group which was not treated with test sample (*p<0.05 vs. control, See FIG. 3)

(44) Accordingly, it has been confirmed that the invention composition showed potent improving effect on the contractility of vagina tissue at 30-300 mg/ml (P<0.001).

(45) TABLE-US-00003 TABLE 3 Contractility according to increased dose of test sample dose (mg/ml) sample N Mean SEM 1 SG3 10 −0.815 0.716 control 6 −0.178 0.398 3 SG3 10 −1.947 0.940 control 6 −0.622 0.428 10 SG3 10 −1.153 0.425 control 6 −0.813 0.451 30 SG3 10 16.173 2.708 control 6 −0.140 0.441 100 SG3 10 31.226 7.015 control 6 −0.647 0.360 300 SG3 10 25.836 4.125 control 6 −0.898 0.374

Experimental Example 1

Brief Clinical Test (1)

(46) The vaginal tablet composition (SG2) prepared in Example was administrated intra-vaginally once a day for 5 days to 100 volunteers consisting of 35 patients suffering from lax vagina syndrome, and 65 normal women ranging from 20 to 50 years who live in Korea and the effect on the vagina contractility of inventive composition was surveyed and determined by using perinometer (peritro9300, Laborie Medical Technologies Canada ULC).

(47) The perinometer (peritro9300, Laborie Medical Technologies Canada ULC) for determining a vaginal pressure has a different size varied with a different pressure, i.e., at 0 cm H.sub.2O: length 8 cm and diameter 26 mm; at 100 cm H.sub.2O, length 8 cm and diameter 30.5 mm. The apparatus surrounded with condom was inserted into the volunteer's vagina to the extent that the tip of apparatus had reached to 7 cm depth of vagina. The volunteer' body was to be relaxed by spreading her legs and relaxing vaginal muscle. After turning on the apparatus, the measures have zeroed in on precisely and probe was inflated by inserting air to the extent that the value had reached to 100 cm H.sub.2O. The measures have zeroed again in on precisely and the vagina of volunteer being cautious with not moving waist or pelvis, has been forced to be strongly constricted and lasted for 5 seconds to determine the contractility of vagina muscle. The volunteers were allowed to have a rest for at least 1 min after repetitive determination and the mean value of the contractility was calculated by determining three times for 1 volunteer.

(48) At the result, it has been confirmed that the internal pressure of vaginal muscle treated with inventive composition was remarkedly increased to about 38% (after 3 days) and about 52% (after 5 days) as can be seen in Table 4.

(49) TABLE-US-00004 TABLE 4 result of vaginal contractility (unit: cmH.sub.20) Before 3 days after the 5 days after the treatment treatment treatment Mean 42.72 58.96 64.98 standard deviation ±12.58 ±13.25 ±13.91

Experimental Example 2

Brief Clinical Test (2)

(50) The vaginal insertion tablet composition (SG5) prepared in Example was administrated externally twice a day for 3 days to 100 volunteers consisting of 35 patients suffering from colpoxerosis disease, and 65 normal women ranging from 20 to 50 years who live in Korea and the effect on the vaginal dryness (A) before and (B) after the treatment with inventive composition was determined. The survey result was categorized into 5 grades according the vaginal dryness after the treatment, i.e., (1) the amount of leukorrhea was much reduced, (2) the amount of leukorrhea was little reduced, (3) the amount of leukorrhea was not changed, (4) the amount of leukorrhea was little increased, (2) the amount of leukorrhea was much increased.

(51) At the result, it has been confirmed that the amount of leukorrhea was increased in more than 83% volunteers after the treatment of inventive composition.

(52) Accordingly, it has been confirmed that the inventive composition is useful in treating colpoxerosis disease, as can be seen in Table 5.

(53) TABLE-US-00005 TABLE 5 test result on colpoxerosis disease grade (1) (2) (3) (4) (5) Number of 3 4 10 64 19 volunteers

(54) Accordingly, it has been proved that the inventive composition can be useful in treating lax vagina syndrome or colpoxerosis disease.

(55) The invention being thus described, it will be obvious that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the present invention, and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims.

INDUSTRIAL APPLICABILITY

(56) The present invention relates to a use of the mixture of a salt and sugar in the manufacture of a medicament employed for treating lax vagina syndrome or colpoxerosis disease in a mammal. As described in the present invention, through various tests, for example, vaginal smooth muscle contractility test using by New Zealand White Rabbit; (Experimental example 1); the effect on the vagina contractility in volunteers by using perinometer (Experimental example 2); and the effect on the colpoxerosis disease in volunteers (Experimental example 3), the inventive combination showed improving effect on the contractility of vagina tissue and colpoxerosis disease. Accordingly, the inventive combination can be useful in treating or preventing lax vagina syndrome or colpoxerosis disease.