KR20200011222A - Composition for improving vagina environment and improving agent having the same - Google Patents

Abstract

Disclosed are a composition for improving vaginal environment and an enhancer comprising the same. The composition for improving vaginal environment according to an embodiment of the present invention is a pulse-type vaginal environment improving composition which changes vaginal environment into an acidic environment by releasing organic acids according to changes in the acidity of women′s vagina. Therefore, through the pulse-type vaginal environment improving composition which does not behave when pH environment in a vagina is weakly acidic and releases organic acids when pH environment in the vagina is alkali, it is possible to create a constant weakly acidic environment.

Description

Composition for improving the disease scene, and an improving agent comprising the same {COMPOSITION FOR IMPROVING VAGINA ENVIRONMENT AND IMPROVING AGENT HAVING THE SAME}

The present invention relates to a disease-directing composition and an improving agent comprising the same, and more particularly, to a disease-directing composition and an improving agent including the same, which can maintain a healthy vaginal environment by maintaining a woman's vaginal environment in an acidic environment. .

Female genitourinary diseases include ovarian cancer, uterine fibroids, posterior uterine uterus, uterine and vaginal prolapse, uterine cancer, chorionic epithelial cancer, cervical dysplasia, cervical cancer, vulvar vaginitis, vaginal fungal disease, bacterial vaginosis, and sexually transmitted diseases. It is reported that most women experience at least one disease during their lifetime.

The genitourinary system of women includes the uterus, vagina, vulva, urethra, etc., anatomical physiological and functional characteristics are susceptible to infection from the outside. In addition, the genitourinary system of women has vaginal mucosa and secretion decreases due to changes in sex hormones due to childbirth and menopause, blood flow decreases, and vaginal wall thinning due to lack of estrogen and bleeding due to sex life in dry vaginal environment. have. For example, because the vagina is rich in nutrients and deeply located in the human body, because of high temperature and humidity, it is easy to invade various strains including bacteria or fungi, which are the main causes of vaginitis, and various diseases are likely to occur. Therefore, it is always advisable to keep the vagina clean and not to be exposed to bacterial infections from the outside.

Particularly, vaginitis is one of the most common diseases of patients who visit gynecologists.Inflammation disease is caused by the destruction of the vaginal mucosa and the growth of various bacteria, parasites and viruses in the vagina. Is released, odors occur and itching causes pain in sexual life. In addition, vaginitis can be a cause of infertility due to fallopian tube damage when chronic, and HPV infection is closely related to cervical cancer. Therefore, it is very important to reduce fatal complications as appropriate prevention, diagnosis and treatment.

The female genitourinary system contains lactobacillus that keeps the genitourinary pH at a weak acidity of 3.5 to 6.5, which prevents the growth of harmful bacteria.In addition to physical damage, stress and hormonal imbalances, Women's urogenital system-related diseases are likely to occur due to bacterial diseases or sexually transmitted diseases. In other words, when the balance of the vaginal pH environment of a woman is broken, it is exposed to various harmful bacteria, for example, prevotelella, etc., so that the vaginal beneficial bacteria, such as Lactobacillus, can be inhabited and confront the harmful bacteria by maintaining the vaginal environment in a weakly acidic environment. It is desirable to create a healthy vaginal environment.

In order to prevent such female diseases and to remove unpleasant odors, vaginal cleaners (cleaning agents) and vulva cleaners are often used. In the case of such a vaginal cleaner, it is simply used as a cleaning agent without considering the pH environment in the vagina, and it seems that there is no research for controlling the pH environment in the vagina.

Patent Document 1: Republic of Korea Patent Publication No. 10-1841137

Embodiments of the present invention are to provide a pulse type disease-lightening composition that can change the vaginal environment to a weak acid environment by releasing an organic acid according to the change in the vaginal acidity.

In addition, through the polymer coating the organic acid, when the intravaginal pH environment is changed to an alkaline environment, the polymer releases the organic acid therein to provide a disease-resistant composition that can form a weakly acidic environment.

In addition, it is intended to provide an agent for improving the disease pathology by adding an additional component to such a pathology improving composition.

According to one embodiment of the present invention, a disease-improving composition for releasing an organic acid according to a change in vaginal acidity of a woman to change the vaginal environment into an acidic environment includes an organic acid and a pH-dependent polymer.

In addition, according to an embodiment of the present invention, the organic acid, acetic acid, adipic acid, formic acid, formic acid, lactic acid, malic acid and malonic acid ( malonic acid) may include any one or more selected from the group consisting of.

In addition, according to one embodiment of the present invention, the pH-dependent polymer is coated with the organic acid, when the acidity of the vaginal acidity of women can be dissolved to release the organic acid inside.

In addition, according to an embodiment of the present invention, the pH-dependent polymer, polymethacrylate (polymethacrylate) (Hypromellose Phthalate), HPMCP (Hypromellose Phthalate), alginate (alginate) and chitosan (chitosan) any one or more selected from the group It may include.

In addition, according to an embodiment of the present invention, it may further include any one or more selected from the group consisting of antimicrobial agents, viscosity regulators and pH regulators.

Disease scene improving agent according to an embodiment of the present invention includes the disease scene improvement composition.

In addition, according to one embodiment of the present invention, the disease improvement composition may be prepared in a granular, powder or liquid form.

Embodiments of the present invention using a pH-dependent polymer containing the organic acid and coating the organic acid, the disease scene improvement composition does not behave when the vaginal acidity is slightly acidic, but behaves when it is changed to alkali to release the internal organic acid. The vaginal environment can be changed to a weakly acidic environment. That is, when the intravaginal pH environment is weakly acidic, a constant weakly acidic environment may be formed through the pulsed disease-directing composition that releases organic acids from alkaline rather than behaving.

In addition, through the disease alleviating agent having a functional by adding an additional component to such a disease improving composition, it is possible to secure additional functions such as antibacterial action as well as improvement of the vaginal pH environment.

1 to 3 are graphs showing the acid release rate of each disease-remediation agent according to an embodiment of the present invention over time by pH.
Figure 4 is a graph comparing the acid release rate of the pathogen improvers according to an embodiment of the present invention.
Figure 5 is a graph comparing the acid release rate of the pathogen improver according to an embodiment of the present invention.

Hereinafter will be described in detail with reference to Examples to help the understanding of the present invention. However, the following examples are merely to illustrate the content of the present invention, the scope of the present invention is not limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art. The invention is not limited to the examples presented herein but may be embodied in other forms.

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for improving a disease scene, and more particularly, to a pulsed disease scene improving composition for releasing an organic acid according to a change in vaginal acidity of a woman to change the vaginal environment into an acidic environment. The pathology improving composition according to an embodiment of the present invention includes an organic acid and a pH dependent polymer.

The pH-dependent polymer is coated with the organic acid, and does not behave when the vaginal acidity is weakly acidic, but behaves when it is changed to alkali, releasing the internal organic acid, thereby changing the vaginal environment to a weakly acidic environment.

That is, when the intravaginal pH environment is weakly acidic, a constant weakly acidic environment may be formed through the pulsed disease-directing composition that releases organic acids from alkaline rather than behaving.

In the present invention, the disease-enhancing composition may release the organic acid inside the polymer when the pH-dependent polymer starts to dissolve when the vaginal acidity of the female is pH 4.5 or more. The pH-dependent polymer releases the internal organic acid as the surrounding environment gradually changes from acidic to alkaline, and in order to maintain the weakly acidic environment, the pH-dependent polymer can slowly prevent the internal organic acid from being weakly changed to alkaline.

The organic acid may be acetic acid, adipic acid, formic acid, lactic acid, malic acid or malonic acid.

The pH dependent polymer may be polymethacrylate, Hypromellose Phthalate (HPMCP), alginate or chitosan.

Polymethacrylate has the basic structural formula of the following formula (1).

[화학식 1]

[Formula 1]

For example, polymethacrylates are Eudragit L 100-55, Eudragit L 30 D-55, Eastacryl 30 D, Kollicoat MAE 30 DP, Kollicoat MAE 100 P, Acryl-EZE, Acryl-EZE 93 A, Acryl-EZE MP, Eudragit L 12.5 P, Eudragit L 12.5, Eudragit L 100, Eudragit S 12.5 P, Eudragit S 12.5, Eudragit S 100 or Eudragit FS 30 D.

Eudragit L 100-55 is supplied in powder form and starts to dissolve from pH 5.5, Eudragit L 30 D-55 is supplied in aqueous dispersion form and starts to dissolve from pH 5.5, Eastacryl 30 D is an aqueous acid solution. (aqueous dispersion) and start to dissolve from pH 5.5, Kollicoat MAE 30 example is supplied in aqueous dispersion form and starts to dissolve from pH 5.5, Kollicoat MAE 100 P is supplied in powder form to pH Begins to dissolve from 5.5, Acryl-EZE is supplied in powder form and begins to dissolve from pH 5.5, Acryl-EZE 93 A is supplied in powder form and starts to dissolve from pH 5.5, Acryl-EZE MP is in powder form To be dissolved from pH 5.5, Eudragit L 12.5 P is supplied in the form of an organic solvent and starts to dissolve from pH 6, and Eudragit L 12.5 is dissolved in an organic solvent. Is fed into the milk and starts to dissolve from pH 6, Eudragit L 100 is supplied in the form of a powder medium and starts to dissolve from pH 6, Eudragit S 12.5 P is fed in the form of an organic solvent and starts to dissolve from pH 7 and Eudragit S 12.5 is supplied in the form of an organic solvent and starts to dissolve from pH 7, Eudragit S 100 is supplied in the form of a powder and starts to dissolve from pH 7, and Eudragit FS 30 D is supplied as an aqueous acid solution and starts to dissolve from pH 7. It exhibits behavior.

HPMCP has a basic structural formula (II).

[화학식 2]

[Formula 2]

The HPMCP may be HPMCP 55S, HPMCP 55 or HPMCP 50.

HPMCP 55S is supplied in powder form and starts to dissolve from pH 5.5, HPMCP 55 is fed in organic solvent form and starts to dissolve from pH 5.5, HPMCP 50 is fed in organic solvent form and starts to dissolve from pH 5 Has HPMCP is a hydroxypropyl methylcellulose (HPMC) series has a certain viscosity, HPMCP 55S has a viscosity of 170cSt, HPMCP 55 is 40cSt, HPMCP 50 has a viscosity of 55cSt.

Alginate may be provided in the form of sodium alginate. Sodium alginate is not soluble in organic solvents, but is slowly dissolved in water to form a viscous colloidal solution. Sodium alginate does not dissolve in acidic solutions below pH 3 and precipitates, exhibits a viscosity of about 20-200 cps at pH 3-7 and a viscosity of about 100 cps at pH 4. Alginate begins to release acid slowly from about pH 3 and strongly from pH 5.

Chitosan has a basic structural formula of Chemical Formula 3 below.

[화학식 3]

[Formula 3]

Chitosan may be provided in the form of Chitosan Hydrochloride. Chitosan hydrochloride, although slightly soluble in water, is easily soluble in ethanol, is also readily soluble in dilute organic acid solutions and hardly soluble in neutral or slightly alkaline solutions above pH 6.5. The solubility of chitosan is lower solubility according to salting effect as the ionic strength of the solution is higher, and the viscosity is higher at low pH, but the viscosity is lower as the pH is higher, thereby increasing the amount of release. Chitosan begins to release acid slowly from about pH 4 and strongly from pH 6. In particular, chitosan is a biodegradable substance, which is harmless to the human body, and is bioadhesive and can be attached to the vaginal wall to continuously release a desired drug (here, an organic acid substance).

In the present invention, the pH-dependent polymer coating and enveloping the organic acid has a viscosity change according to pH, and has a high viscosity in an acidic environment having a low pH, thereby strongly holding the organic acid, so that the degree of release of the internal organic acid is weak and the pH increases. Therefore, the change in the alkaline environment has a low viscosity to have a low viscosity to reduce the force holding the organic acid to increase the amount and release rate of the internal organic acid.

That is, the vaginal environment-improving composition of the present invention maintains high viscosity in an acidic environment with low pH to prevent or minimize the amount of internal organic acid released, and gradually releases the internal organic acid as the pH increases to an alkaline environment, thereby gradually releasing the internal organic acid in the vaginal environment. Can be maintained in an acidic environment.

The pH dependent polymer may be used by mixing one or more of the above examples so as to have an appropriate viscosity change depending on the pH. For example, alginate and chitosan can be mixed and used.

In the present invention, the disease modifying composition may further include an antimicrobial agent, a viscosity adjusting agent and a pH adjusting agent.

Antimicrobial agents, viscosity regulators, pH regulators may be used widely used products, for example, chitosan and alginate as a pH regulator may be used, but is not limited thereto.

The disease scene improving agent of the present invention may be prepared including the above disease scene improving composition, and the disease scene improving composition may be prepared in granular, powder or liquid form.

The disease-enhancing agent may be prepared in various forms such as powder, liquid, ointments, pastes, creams, vaginal tablets and the like. In the case of powder or liquid form, it can be transformed into an ointment form through the addition of additional viscosity and pH adjusters.

 Hereinafter, the present invention will be described in more detail with reference to examples of the disease-directing composition and its preparation method.

Example (Production of composition)

Organic Acid

Organic acids 1 Acetic acid Organic acids 2 Adipic acid Organic acids 3 Formic acid Organic acids 4 Lactic acid Organic acids 5 Malic acid Organic acids 6 Malonic acid

2. pH dependent polymer

Polymethacrylate Polymer 1 Eudragit L 100-55 Polymer 2 Eudragit L 30 D-55 Polymer 3 Eastacryl 30 d Polymer 4 Kollicoat MAE 30 DP Polymer 5 Kollicoat MAE 100 P Polymer 6 Acryl-EZE Polymer 7 Acryl-EZE 93 A Polymer 8 Acryl-EZE MP Polymer 9 Eudragit L 12.5 P Polymer 10 Eudragit L 12.5 Polymer 11 Eudragit L 100 Polymer 12 Eudragit S 12.5 P Polymer 13 Eudragit S 12.5 Polymer 14 Eudragit S 100 Polymer 15 Eudragit FS 30 D HPMCP Polymer 16 HPMCP 55S Polymer 17 HPMCP 55 Polymer 18 HPMCP 50 Carbomer Polymer 19 Carbomer Alginate Polymer 20 Sodium Alginate Chitosan Polymer 21 Chitosan Hydrochloride

3. Manufacturing Method

(1) Preparation Example 1

After dissolving 200 mg of Eudragit L 100-55 (Polymer 1) in 2.5 ml of propanol, 200 mg of Lactic acid was added to the mixture, and then sufficiently mixed. Lactic acid coated with Eudragit L in the form of microspheres was obtained. Thereafter, the resultant was washed three times with a buffer solution having a pH of 3 or more and dried, and the dried product was stirred with a hydrogel (lactic acid concentration of 1% to 5%) to adjust to 400 mPas, pH 3.5 or more to prepare a disease-enhancing agent. .

(2) Preparation Example 2

After dissolving 100 mg of Eudragit L 100-55 (Polymer 1) in 2.5 ml of ethanol, 200 mg of Lactic acid was coated with Eudragit L 100-55 in powder form using a fluidized bed granulator to obtain Lactic acid coated with Eudragit L 100-55. Thereafter, the obtained product was stirred with a hydrogel (lactic acid concentration of 1% to 5%) to adjust to 400 mPas, pH 3.5 or more to prepare a disease-enhancing agent.

(3) Preparation Example 3

Lactic acid (pH 3.5) was prepared with a concentration of 1% of lactic acid, and chitosan hydrochloride (polymer 21) was added to a 1% w / v chitosan mixture in a stirrer to prepare Lactic acid in the form of the clathrate contained in the chitosan composite gel. Obtained. Thereafter, the obtained product was stirred with a hydrogel (lactic acid concentration of 1% to 5%) to adjust to 400 mPas, pH 3.5 or more to prepare a disease-enhancing agent.

(4) Preparation Example 4

1.5 mg of lactic acid was dissolved in a solvent (water) having a pH of 6.5 or higher, and 50 mg of sodium alginate (polymer 20) was added thereto, stirred at a speed of 50 rpm with a weak acidity of pH 3, and mixed. After complete dissolution of sodium alinate, 50 mg of Chitosan hydrochloride (polymer 21) was slowly added and stirred at a speed of 65 rpm to yield cross-linked Lactic acid with chitosan and / or alginate. Thereafter, the obtained product was stirred with a hydrogel (lactic acid concentration of 1% to 5%) to adjust to 400 mPas, pH 3.4 or higher to prepare a disease-enhancing agent.

(5) Preparation Example 5

Add 10 mg of Lactic acid to 10 ml of Eudragit L 30 D-55 (Polymer 2) solution, stir, and mix 10 g of Florite R (Calcium Silicate) to the mixture, use a coalescer to dry and dry Eutect L-coated Lactic acid. Obtained. Thereafter, the obtained product was stirred with a hydrogel (lactic acid concentration of 1% to 5%) to adjust to 400 mPas or more and pH 3.5 or more to prepare a disease-enhancing agent.

Experimental Example

Experimental Example  One

In order to confirm the behavior in an acidic environment, according to the dissolution test method of the Korean Pharmacopoeia, 100 mL of pH 1.2 solution was added to an immersion cell in combination with paddle apparatus. 10 g of each species was applied to the immersion cell wall and the dissolution test was performed. The sample collected over time was filtered to analyze the residual Lactic acid content by HPLC, and organic acid analysis was analyzed by citing the literature (Z Lebensm Unters Forsch (1983) 176: 440M43). The change in the release of lactic acid was observed.

Experimental Example  2

In order to confirm the behavior in an acidic environment, according to the dissolution test method of the Korean Pharmacopoeia, 100 mL of pH 4.5 solution was added to an immersion cell in combination with paddle apparatus. 10 g of each species was applied to the immersion cell wall and the dissolution test was performed. Samples collected over time were filtered to analyze the residual content of lactic acid by HPLC. Then, the change in the release of lactic acid with time was observed.

Experimental Example  3

In order to confirm the behavior in an acidic environment, according to the dissolution test method of the Korean Pharmacopoeia, 100 mL of pH 6.8 liquid was added to an immersion cell in combination with paddle apparatus. 10 g of each species was applied to the immersion cell wall and the dissolution test was performed. Samples collected over time were filtered to analyze the residual content of lactic acid by HPLC. Then, the change in the release of lactic acid with time was observed.

Experimental Example  4

In order to confirm the behavior in an acidic environment, according to the dissolution test method of the Korean Pharmacopoeia, 250 mL / 250 mL (2-step elution method) of pH 1.2 to 6.8 was added to a paddle over disc apparatus. 20 g of each of two disease-enhancing agents prepared according to the present invention were injected into a Reciprocating disk and the dissolution test was performed. Samples collected over time were filtered to analyze the residual content of lactic acid by HPLC. Since the release of lactic acid over time was observed.

1 to 3 are graphs showing the acid release rate of each disease-remediation agent according to an embodiment of the present invention over time by pH. Figure 4 is a graph comparing the acid release rate of the pathogen improvers according to an embodiment of the present invention. Figure 5 is a graph comparing the acid release rate of the pathogen improver according to an embodiment of the present invention.

More specifically, FIG. 1 shows the acid release rate over time under pH 1.2 conditions, FIG. 2 shows the acid release rate over time under pH 4.5 conditions, and FIG. 3 shows the acid release rate over time under pH 6.8 conditions. Figure 4 shows the acid release rate according to the time and pH conditions for comparing the Preparation Example 2 and Preparation Example 4.

Improvement agents of Preparation Examples 1 to 5 can be seen that the amount of release of lactic acid gradually increases with time, and the rate of increase of the amount of lactic acid is increased in a weak acidic to alkaline environment (basic environment) rather than an acidic environment with low pH. Able to know. That is, it was confirmed that the release rate of lactic acid was higher in alkaline than in acid. Looking at the lactic acid release rate of Preparation Example 3 and Example 4, the release rate of Preparation Example 3 is generally large, which is Preparation Example 3 using chitosan as a pH-dependent polymer and Preparation Example 4 simultaneously with alginate as a pH-dependent polymer as well as chitosan Since it is used, the release rate can be controlled more slowly by the action of alginate, and the release time can be controlled to release for a long time.

Figure 5 shows the acid release rate with time of Preparation Example 2 and Preparation Example 4 of the present invention while changing the pH from 1.2 to 6.8.

Referring to Figure 5, as confirmed the release pattern of the improver according to Preparation Example 2 and Preparation Example 4, in the case of Preparation Example 2 has a characteristic that the release rate is rapidly increased when the change to the alkaline environment in the acidic environment is maintained. Able to know. In case of Preparation Example 4, some acid is continuously released from the acidic environment and the release rate increases when the change to the alkaline environment, but it does not show a rapid release rate increase characteristic compared to Preparation Example 2, and in case of Preparation Example 2, the acid release of the improver is alkali After about 6 hours in the environment, the release rate was about 100% .However, in Preparation Example 4, all the acids were not released even after 6 hours, and the acid was still released and the acid was continuously released for more than 12 hours. Can be.

Therefore, according to the disease-directing composition and improving agent of the present invention, the vaginal environment can be continuously maintained in an acidic environment. In addition, in order to maintain the vaginal environment continuously in the acidic environment, the release of the acid component can be continued for more than 6 hours instead of ending in a short period of time. Especially, the combination of the pH-dependent polymer allows the organic acid component to be continuously released for a long time. It is possible to perform the function as a pulsed disease-enhancing composition that releases the organic acid to maintain the acidic environment whenever it changes from an acidic environment to an alkaline environment.

As described above, the exemplary embodiments of the present invention have been described, but the present invention is not limited thereto, and a person skilled in the art does not depart from the concept and scope of the following claims. It will be appreciated that various changes and modifications are possible in the following.

Claims (7)

A pulse type disease improvement composition for releasing an organic acid according to a change in vaginal acidity of a woman to change the vaginal environment into an acidic environment,
Pathology improving composition comprising an organic acid and a pH dependent polymer. The method of claim 1,
The organic acid is at least one selected from the group consisting of acetic acid, adipic acid, formic acid, lactic acid, malic acid and malonic acid. Disease scene improvement composition comprising a. The method of claim 1,
The pH-dependent polymer is coated with the organic acid, and dissolves when the vaginal acidity of the female pH 4.5 or more, characterized in that to release the organic acid inside the disease-cure composition. The method of claim 1,
The pH dependent polymer,
Polymethacrylate (polymethacrylate), HPMCP (Hypromellose Phthalate), alginate (alginate) and chitosan (chitosan) composition for improving the disease scene, characterized in that it comprises any one or more selected from the group consisting of. The method of claim 1,
An antiviral disease improving composition further comprising any one or more selected from the group consisting of an antimicrobial agent, a viscosity modifier, and a pH adjuster. A disease path improving agent comprising the disease path improving composition of any one of claims 1 to 5. The method of claim 6,
The disease scene improving composition is a disease scene improving agent, characterized in that prepared in a granular, powder or liquid form.

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