KR100896453B1 - Pelargonium sidoides Syrup - Google Patents

Abstract

The present invention relates to pelargonium sidoides syrup which is used as a therapeutic agent for acute or chronic infectious diseases. The present invention can significantly improve the bitter taste and unpleasant odor caused by drugs compared to the liquid of the conventional Pelargonium sidoides extract, so that the patient's compliance with the drug can be improved and easily administered to children or the elderly. In addition, the present invention provides a method for analyzing the content of the Pelargonium sidoides extract, which is responsible for drug expression, to prepare a syrup having a titer above the exact standard, and in fact, the titer of the manufactured syrup product also maintains a constant level. It became possible to formulate into quantitative syrups. Furthermore, due to the quantitative analysis of the Pelargonium sidoides extract of the present invention, it is possible to measure the content in the syrup containing the Pelargonium sidoides extract, which is excellent in reproducibility and high reliability through a relatively simple operation. Has the advantage of showing.

Pelargonium sidoides, syrup, extraction, di-sorbitol, quantitative analysis, epicatechin, absorbance

Description

Pelargonium sidoides Syrup

1 is a graph showing the relationship between the concentration and absorbance of the Pelargonium sidoides extract.

The present invention is used to treat Pelargonium sidoides ( Pelargonium) sidoides ) on the syrup.

Extracts from the roots of the species of pelagium , such as the pelargonium sidoides and the pelargonium reniforme, which are native to southern Africa, include diarrhea, gastrointestinal complaints, dysmenorrhoea, and liver disease ( It has been traditionally widely used in Africa as a therapeutic agent for liver diseases (Watt, C. (1962) Medicinal and poisonous plants of southern and eastern Africa , Livingstone, Edinburgh, London, S. 449-455). In addition, it is known to be excellent for the treatment of respiratory diseases, especially tuberculosis.

Pelargonium sidoides extract, originally known as a traditional medicinal herb in South Africa, is known to be used in other regions, specifically in central Chile and Mexico. That is, in the region, the astringent function of the extract of Pelargonium sidoides was used to treat diarrhea and various gastrointestinal syndromes. These effects are known to be attributed to tannin, a constituent of the extract (Jose San Martin, A. (1983) Econom . Bot , 37 , 216-227. INI (1994) Atlas de las plantas de la medicina tradicional mexicans (Instituto Nacional Indigenista, Hrsg.) Vol II, Av. Revolucion no 1279, Col. Tiacopac, Mexiko, S. 667 und 950).

Furthermore, in the early 20th century in the United States, the root extract of Pelargonium sidoides is known as Umckaloabo in the upper airway (Kauffer, HJ (1915) Dental Cosmos 57 , 1366), such as rhinopharyngitis, tonsillitis It has been used in the treatment of tonsillitis, sinusitis, brochitis and the like.

This effect is known to be due to the antimicrobial effect of Pelargonium sidoides extract.

More specifically, coumarin experiments show that there is moderate cytotoxicity against GLC4, lung cancer cells, and COLO320 cells, and this cytotoxic effect is wholly dependent on the nature and position of the substituents in the aromatic ring. In the agar dilution test, experiments with coumarin and tannin compounds for antimicrobial action against various Gram-positive and Gram-negative bacteria showed moderate bacteriostatic effects. Minimal Inhibitory Concentration (MIC) values range from 200 to 2000 μg / ml (for coumarins) and 500 to 2000 μg / ml (for monomer tannin precursors), with highly antimicrobial coumarin trioxide, 4 Oxidized materials are representative. This clear antimicrobial activity is seen in the extract of Pelargonium sidoides, especially the extracts of roots and leaves, water is the largest antibacterial effect as a solvent. (Kayser, O. (1997) Phenolic constituents of Pelargonium sidiodes DC. and studies of the efficacy of the Umcka plant material ( Pelargonium sidiodes DC. and Pelargonium reniforme CURT .) Doctorial dissertion, Berlin Free University.)

On the other hand, Pelargonium sidoides extract is useful for the treatment of acute or chronic infectious diseases by affecting the immunomodulatory effect.

Specifically, Pelargonium sidoides extract has been reported to increase TNF-α, INF-β, nitric oxide (NO) synthesis (H. Kolodziej et al., Phytomedicine 10 (Suppl. 4) , 18-24 (2003)).

In addition, coumarin derived from Pelargonium sidoides extract has been shown to exhibit immunostimulatory effects in various experimental models. Specifically, in the intracellular Leishmania infection model, these substances showed moderately structure-dependent actions in relation to oxygen-dependent immune defense mechanisms, in particular intracellular infection via NO-mediated NO production mediated by simple coumarins. Moderate defensive stimulation of ROS increases with increasing oxygen production. In addition, gallic acid (gallic acid), which is another component of the extract, is an excellent derivative, and its activity is due to a high concentration of nitric oxide radicals. (Kayser, O. (1997) Phenolic constituents of Pelargonium sidiodes DC. and studies of the efficacy of the Umcka plant material ( Pelargonium sidiodes DC. and Pelargonium reniforme CURT .) Doctorial dissertion, Berlin Free University.)

These pelargonium sidoides extracts have been shown to be effective in acute or chronic infections, especially infections of the respiratory tract or ear throat, such as bronchitis, sinusitis, tonsillitis, nasopharyngitis.

On the other hand, syrups are easy to administer to children or elderly people who lack the ability to swallow tablets, have a rapid drug effect compared to tablets, and bioavailability differences that may be caused by differences in drug solubility of the subjects when tablets are administered. It can also reduce the benefits that the drug can be kept constant. In addition, oral administration can significantly improve the bitter taste and unpleasant odor caused by the drug, thereby increasing the patient's compliance with the drug can be easily administered to children and the elderly.

However, in the case of Pelargonium sidoides extract, the content analysis method of the extract responsible for expression of the drug is not established, making it difficult to prepare a syrup having a titer above the exact standard, and in fact, the titer of the manufactured syrup product also has a constant level. It was impossible to maintain, and therefore no formulation into quantitative syrup was achieved.

The present invention has been made to solve the above problems, to provide a composition as a syrup preparation for the treatment of acute or chronic infectious diseases, having a constant titer above the exact standard, and containing a pelargonium sidoides extract. It is done.

The composition for the treatment of acute or chronic infectious diseases of the present invention is 0.01-0.1 M of di-sorbitol di-mannitol solution (di-sorbitol: di-mannitol) in addition to 100.00 parts by weight of Pelargonium sidoides extract and 117 to 217 parts by weight of purified water. Weight ratio of 4 to 6: 1) or 0.01 to 0.1 M of di-sorbitol aqueous solution, characterized in that it comprises 285 to 530 parts by weight.

In addition, the composition is a group consisting of 0.48 to 0.89 parts by weight of preservatives, 0.04 to 0.08 parts by weight of colorant, 2.52 to 4.67 parts by weight of fragrance, 1.63 to 3.03 parts by weight of pH adjuster, and mixtures thereof, per 100.00 parts by weight of pelargonium sidoides extract It is preferable to further include an additive selected from.

In addition, the preservative may be potassium sorbate.

In addition, the colorant may be a disodium salt of 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl) azo] -2-naphthalenesulfonic acid.

In addition, the fragrance may be a cherry or menthol (menthol) extract.

In addition, the pH adjusting agent may be citric acid.

In addition, the pH of the composition is preferably 2.5 to 4.5.

In addition, the total amount of phenol in the composition is preferably 0.06 to 0.5 parts by weight per 100 parts by weight of the Pelargonium sidoides extract.

In addition, the Pelargonium sidoides extract is preferably extracted from the root of the Pelargonium sidoides.

In addition, the Pelargonium sidoides extract may be extracted with a solvent selected from the group consisting of water, methanol, ethanol, propanol, butanol, and mixtures thereof.

In addition, the total amount of phenol in the composition preferably comprises the following steps:

(A) 40 to 60 parts by weight of 15 to 30% by weight of ethanol aqueous solution, 6 to 9 parts by weight of Floin Ciocalteus phenol reagent, 10 to 20% by weight, per 1 part by weight of Pelargonium sidoides extract 40 to 60 parts by weight of an aqueous sodium carbonate solution, and 15 to 40 parts by weight of water, and the sample solution preparation step of taking the supernatant as a sample solution by centrifuging the mixed solution,

(B) 8 to 12 parts by weight of 15 to 30% by weight of ethanol aqueous solution, 1 to 2 parts by weight of Floin Ciocalteus phenol reagent, 10 to 20% by weight, per 1 part by weight of epipicchin ethanol solution 8 to 12 parts by weight of an aqueous sodium carbonate solution, and 3 to 8 parts by weight of water, the standard solution preparation step of taking the supernatant as a standard solution by centrifuging the mixed solution, and

(C) measuring the absorbance of the sample solution and the standard solution using water as a control solution, and

(D) calculating the total amount of phenol as epicatechin by the following equation (1):

Where Et is the absorbance of the test liquid,

Es is the absorbance of the standard solution,

V is the volume of the sample solution measured in ml,

S is the mass of the standard solution measured in mg.

In addition, the mixture may further include the step of standing at room temperature for 10 to 30 minutes before centrifugation.

In addition, the centrifugation is preferably performed for 5 to 20 minutes.

In addition, the absorbance is preferably measured at 720 nm.

In addition, the 15 to 30% by weight of the ethanol aqueous solution is preferably prepared by diluting 95 to 96% by weight of ethanol aqueous solution and water in a volume ratio of 1: 2 to 5.

In addition, the infection may be an upper respiratory tract infection.

In addition, the infection may be an infection of the respiratory system or the ear throat.

In addition, the infection may be bronchitis, sinusitis, tonsillitis, nasopharyngitis.

In addition, the formulation of the therapeutic composition is preferably a syrup.

Hereinafter, preferred embodiments of the present invention will be described in detail. In addition, in the following description, many specific details such as specific components are disclosed, which are provided to help a more general understanding of the present invention, and it is common in the art that the present invention may be practiced without these specific details. It is self-evident to those who have knowledge of the world. In describing the present invention, when it is determined that a detailed description of a related known function or configuration may unnecessarily obscure the subject matter of the present invention, the detailed description thereof will be omitted.

The syrup containing Pelargonium sidoides extract for the treatment of acute or chronic infectious diseases of the present invention is 0.01-0.1 M of di-sorbitol di-mannitol solution in addition to 100 parts by weight of Pelargonium sidoides extract and 117-217 parts by weight of purified water ( Weight ratio of di-sorbitol to di-mannitol = 4 to 6: 1) or 285 to 530 parts by weight of a di-sorbitol aqueous solution of 0.01 to 0.1 M.

The syrup composition of the present invention can be said to be the first feature that a di-sorbitol di-mannitol solution or a di-sorbitol aqueous solution is used as a sweetening agent.

Fructose or sugar, which has conventionally been used as a sweetener for the preparation of syrups, affects the quantitative analysis of Pelargonium sidoides which will be described later. Specifically, the pelargonium sidoides extract, which is the main active ingredient of the syrup of the present invention, measures the content by the total amount of phenol as epicatechin. However, as the fructose or sugar absorbs the same wavelength and affects the absorbance, it is impossible to measure the total phenol amount, and therefore it is difficult to apply to the present invention.

The inventors sought new sweeteners to replace them and found that D-sorbitol did not absorb this wavelength. Furthermore, it was confirmed that di-sorbitol di-mannitol liquid, which is a mixture with a small amount of D-mannitol, also hardly absorbed the wavelength, and thus, it was adopted as a sweetener of the present invention.

The content of the sweetener of the present invention is preferably 285 to 530 parts by weight per 100 parts by weight of the Pelargonium sidoides extract. If the content is less than 285 parts by weight, the sweetness is less so that the palatability, especially for infants and children, can be significantly reduced, and if it exceeds 530 parts by weight it may be too sweet to reduce the palatability.

The present invention further comprises a variety of ingredients in addition to the sweetener, a preservative 0.48 to 0.89 parts by weight, colorant 0.04 to 0.08 parts by weight, fragrance 2.52 to 4.67 parts by weight, pH adjuster 1.63 to 3.03 parts by weight, and mixtures thereof It may include an additive selected from.

The preservative is added to prevent microbiological contamination of the syrup of the present invention, and the sweetener has excellent potassium sorbate (Potassium Sorbate), which is excellent in stability without affecting the analysis of the pelargonium sidoides extract, such as fructose or sugar. desirable. The amount of the potassium sorbate is preferably 0.48 to 0.89 parts by weight per 100 parts by weight of Pelargonium sidoides extract, if less than 0.48 parts by weight of the syrup of the present invention is likely to be contaminated, if it exceeds 0.89 parts by weight May cause unexpected side effects.

In addition, in order to increase the acceptability visually and olfactoryly, it is preferable to add 0.04 to 0.08 parts by weight of colorant and 2.52 to 4.67 parts by weight of fragrance. In the present invention, 6-hydroxy-5-[(2-meth Methoxy-5-methyl-4-sulfophenyl) azo] -2-naphthalenesulfonic acid disodium salt (Korea Food and Drug Administration Notification No. 2000-66 Red No. 40) and cherry or menthol extract as fragrance It is desirable to.

In addition, it is preferable that the syrup composition for treating infectious diseases of the present invention further comprises 1.63 to 3.03 parts by weight of a pH adjuster. Since the pH of the Pelargonium sidoides extract used as a traditional medicine is acidic, it is preferable to adjust the pH of the syrup of the present invention to acidic, and particularly preferably 2.5 to 4.5. The pH adjuster used in the present invention is more preferably citric acid that does not affect the analysis of Pelargonium sidoides extract.

The Pelargonium sidoides extract is more preferably extracted from the root of Pelargonium sidoides, and the extraction solvent is preferably selected from water, methanol, ethanol, propanol, butanol, and mixtures thereof.

On the other hand, the syrup composition of the present invention requires a quantitative analysis method having a direct relationship with the titer in order to manage the titer of Pelargonium sidoides extract, which is a pharmaceutical component, to a higher level than the correct level and to obtain reproducible results. It is another major feature that the present invention is characterized by such quantitative analysis.

The quantitative analysis of the Pelargonium sidoides extract begins with the preparation of a sample solution containing the extract of Pelargonium sidoides and a standard solution as a base compared thereto.

First, all of the Pelargonium sidoides extract to be analyzed is included as long as it is a substance containing the extract of the Pelargonium sidoides irrespective of its formulation, and in the present invention, a syrup containing the extract is particularly preferable.

40 to 60 parts by weight of 15 to 30% by weight of an ethanol aqueous solution, 6 to 9 parts by weight of a Floin Ciocalteus phenol reagent, and 10 to 20% by weight of an aqueous sodium carbonate solution of 40 to 60 parts by weight of the extract Parts and 15 to 40 parts by weight of water are mixed.

Here, the 15 to 30% by weight of the ethanol aqueous solution is preferably prepared by diluting 95 to 96% by weight of ethanol aqueous solution and water in a volume ratio of 1: 2 to 5.

The mixed solution is then centrifuged and the supernatant taken as the sample solution.

At this time, the centrifugation is preferably performed for 5 to 20 minutes.

In particular, in the present invention, it is more preferable to further include the step of leaving the mixture at room temperature for 10 to 30 minutes before centrifugation in terms of improving the reproducibility of the analysis results.

The epicatechin standard solution is prepared separately from the sample solution. First, 8 to 12 parts by weight of 15 to 30% by weight of an ethanol aqueous solution of 15 to 30% by weight of the epicatechin ethanol solution of moderately diluted epicatechin with 15 to 30% by weight of ethanol solution, 1 to 2 parts by weight of a polline sycartheus phenol reagent , 8 to 12 parts by weight of an aqueous 10-20% by weight sodium carbonate solution, and 3 to 8 parts by weight of water.

Thereafter, the stationary step and the centrifugation step are the same as in the sample preparation step.

Then, the absorbance is measured by using the prepared sample solution and the standard solution as the control solution, the measurement wavelength is most preferably carried out at 720 nm.

Finally, the content of Pelargonium sidoides is determined by calculating the total amount of phenol as epicatechin by the following equation:

[Equation 1]

Where Et is the absorbance of the test liquid,

Es is the absorbance of the standard solution,

V is the volume of the sample solution measured in ml,

S is the mass of the standard solution measured in mg.

In the syrup composition of the present invention, it is preferable that the total phenol amount as epicatechin thus measured is 0.01 to 0.1 parts by weight per 100 parts by weight of the syrup composition. If the total amount of phenol is less than 0.01 parts by weight may not be sufficient to treat the infection, if it exceeds 0.1 parts by weight there is a disadvantage in economic efficiency compared to the degree of drug expression.

EMBODIMENT OF THE INVENTION Hereinafter, the Example of this invention is described.

Example

Example  1: Pelargonium Shidoidesu  Preparation of Extract

100 g of dried root of Pelargonium sidoides was chopped into small pieces (95 cm or more in 1 cm or less), wetted with 200 ml of 35 wt% ethanol aqueous solution, and then extracted by adding 800 ml of 5.3 wt% ethanol aqueous solution. . The obtained residue was compressed again, and the obtained liquid was mixed with the firstly obtained extract, filtered, and heated at 118 to 122 ° C. for 5 to 30 seconds to obtain the pelargonium sidoides extract of the present invention.

Example  2: preparation of syrup

17.16 g of the Pelargonium sidoides extract of Example 1, 0.04 M of di-sorbitol di-mannitol solution (weight ratio of di-sorbitol to di-mannitol = 5: 1) in a 250 ml container of 70.00 g of potassium sorbate 0.117 g, disodium salt of 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl) azo] -2-naphthalenesulfonic acid (KFDA No. 2000-66 Red 40 ) Syrup of the present invention was prepared by adding and mixing 0.010 g, cherry essence (Seoul N. C.), 0.400 g of citric acid, and adding purified water to make 100 ml.

Example  3: Sample  pharmacy

200 μl of the syrup of Example 2 and 96% by weight of an ethanol solution were mixed with purified water and 1: 3, and 10 ml of diluted ethanol diluent, 1.5 ml of Pauline Ciocalceus phenolic reagent, and 10 ml of sodium carbonate solution were added to a 25 ml flask. Purified water was added and the total amount was 25 ml. The mixture was left at room temperature for 20 minutes, then centrifuged for 10 minutes, and the supernatant was taken as a sample solution.

Example  4: Standard Solution

10 mg of epicatechin was collected and placed in a 20 mL flask, and 96% by weight of an ethanol solution was mixed with purified water and diluted 1: 3 to dilute ethanol dilution to make the whole amount 20 ml. 1 ml of the solution was taken and the distillation of the ethanol was added again to make 10 ml of the total amount, where 1 ml was taken. 1 mL of the last solution taken, 10 mL of the ethanol dilution solution, 1.5 mL of the Pauline Sialcartheus phenol reagent, and 10 mL of an aqueous sodium carbonate solution were rinsed into a 25 mL flask, and purified water was added to make 25 mL. The mixture was left at room temperature for 20 minutes, then centrifuged for 10 minutes, and the supernatant was taken as a standard solution.

Example  5: absorbance measurement

In the sample solution of Example 3 and the standard solution of Example 4, absorbance (Agilent Co., Model 8453) was measured at a total length of 10 mm and a wavelength of 720 nm using water as a control solution.

As a result of the measurement, the syrup of Example 2 showed that the total amount of phenol as epicatechin was 25.6 mg on average, meeting the total amount of phenol of the present invention.

Test Example : Toxicity test

In order to determine the acute toxic effect of the Pelargonium sidoides extract of Example 1, the extract was orally administered to rats in varying amounts. As a result, a general state change was not observed at 10 and 20 ㎖ / kg, but at 30 ㎖ / kg showed decreased activity and air conditioning disorder. At 40 ml / kg, the experimental animals fell within 10 to 15 minutes after the drowsiness occurred, but recovered from the unconscious state after 2 to 4 hours. First mortality occurred at 45-50 ml / kg and the remaining survivors recovered after 12-14 hours. The LD ₅₀ for the extract of Example 1 was found to be 48.5 ml / kg.

The syrup based on the Pelargonium sidoides extract of the present invention is based on the Pelargonium sidoides extract, which has been used as a traditional medicine for a long time. The drug is also the same as the original Pelargonium sidoides extract.

Although the above has been illustrated and described with respect to the preferred embodiments of the present invention, the present invention is not limited to the specific embodiments described above, those skilled in the art without departing from the gist of the present invention various modifications Of course, implementation is possible. Therefore, the scope of the present invention should not be construed as being limited to the above embodiments, but should be defined by the claims below and equivalents thereof.

Syrup containing the Pelargonium sidoides extract of the present invention can significantly improve the bitter taste and unpleasant odor caused by the drug compared to the liquid of the conventional Pelargonium sidoides extract, so that the patient's compliance with the drug is increased It can be easily administered to older people.

In addition, the present invention provides a method for analyzing the content of the Pelargonium sidoides extract, which is responsible for drug expression, to prepare a syrup having a titer above the exact standard, and in fact, the titer of the manufactured syrup product also maintains a constant level. It became possible to formulate it into a quantitative syrup.

Furthermore, due to the quantitative analysis of the Pelargonium sidoides extract of the present invention, it is possible to measure the content in the syrup containing the Pelargonium sidoides extract, which is excellent in reproducibility and high reliability through a relatively simple operation. Has the advantage of showing.

Claims (19)

100 parts by weight of Pelargonium sidoides extract; 117 to 217 parts by weight of purified water; Di-sorbitol di-mannitol solution of 0.01 to 0.1 M (weight ratio of di-sorbitol to di-mannitol = 4 to 6: 1) or 285 to 530 parts by weight of a di-sorbitol aqueous solution of 0.01 to 0.1 M; Potassium sorbate 0.48 to 0.89 parts by weight; 0.04-0.08 parts by weight of disodium salt of 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl) azo] -2-naphthalenesulfonic acid; 2.52 to 4.67 parts by weight of cherry or menthol extract; And Citric Acid 1.63 to 3.03 parts by weight Including, pH is 2.5 to 4.5, The Pelargonium sidoides extract is a solvent selected from the group consisting of water, methanol, ethanol, propanol, butanol, and mixtures thereof, which is extracted from the root of Pelargonium sidoides, A composition for the treatment of acute or chronic upper respiratory tract infections, including bronchitis, sinusitis, tonsillitis, or nasopharyngitis. delete delete delete delete delete delete The method of claim 1, The total phenol amount of the composition is 0.01 to 0.1 parts by weight per 100 parts by weight of the therapeutic composition for the treatment of acute or chronic upper respiratory infection. delete delete The method of claim 8, The total phenolic amount of the composition is a composition for the treatment of acute or chronic upper respiratory infection, characterized in that the analysis by the following steps: (A) 40 to 60 parts by weight of 15 to 30% by weight of ethanol aqueous solution, 6 to 9 parts by weight of Floin Ciocalteus phenol reagent, 10 to 20% by weight, per 1 part by weight of Pelargonium sidoides extract 40 to 60 parts by weight of an aqueous sodium carbonate solution, and 15 to 40 parts by weight of water are mixed, and the mixture is allowed to stand for 10 to 30 minutes at room temperature, followed by centrifugation to prepare a sample solution for taking a supernatant as a sample solution. (B) 8 to 12 parts by weight of 15 to 30% by weight of ethanol aqueous solution, 1 to 2 parts by weight of Floin Ciocalteus phenol reagent, 10 to 20% by weight, per 1 part by weight of epipicchin ethanol solution 8 to 12 parts by weight of an aqueous sodium carbonate solution, and 3 to 8 parts by weight of water, the mixture is allowed to stand at room temperature for 10 to 30 minutes and then centrifuged to prepare a standard solution taking the supernatant as a standard solution, and (C) measuring the absorbance of the sample solution and the standard solution using water as a control solution, and (D) calculating the total amount of phenol as epicatechin by the following equation (1): [Equation 1]

Where Et is the absorbance of the test liquid, Es is the absorbance of the standard solution, V is the volume of the sample solution measured in ml, S is the mass of the standard solution measured in mg. delete delete delete delete delete delete delete A syrup formulation for the treatment of acute or chronic upper respiratory tract infections, comprising the therapeutic composition of claim 1, 8, or 11.

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