A fragrant tea formula for inhibiting gonadotropin secretion and its preparation method

Abstract

This invention discloses a herbal formula for inhibiting gonadotropin secretion and its preparation method, relating to the field of traditional Chinese medicine preparation. It comprises the following ingredients by weight: 10-15g of vine tea, 5-8g of citronella, 5-8g of rehmannia root, 5-8g of anemarrhena rhizome, 5-8g of phellodendron bark, 8-10g of paper mulberry fruit, 8-10g of tangerine seed, 5-8g of turmeric, and 5-8g of jujube. The formula uses nine medicinal herbs, including vine tea, citron, and rehmannia root, as raw materials to produce a compressed herbal tablet. This ensures that the growth rate of children treated remains at a normal level, consistent with the normal growth rhythm of children of the same age. Furthermore, it is formulated as an oral instant-dissolving tablet, which can be ground and mixed with warm water, milk, or juice for oral administration, eliminating the need for injection and reducing children's fear and resistance to injections.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation, specifically to a fragrant tea formula for inhibiting gonadotropin secretion and its preparation method. Background Technology

[0002] With changes in modern lifestyles, adjustments in children's nutritional intake, and exposure to environmental endocrine disruptors, the incidence of precocious puberty and related endocrine disorders in children is increasing year by year. Excessive secretion of gonadotropins is one of the core physiological mechanisms causing precocious puberty in children. It may lead to advanced bone age, a shortened growth cycle, and consequently affect final adult height. It may also have adverse effects on children's psychological development. Therefore, developing safe and effective interventions to inhibit gonadotropin secretion has become an important research direction in pediatric medicine and traditional Chinese medicine.

[0003] Gonadotropins (such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are secreted by the pituitary gland. Abnormally elevated levels can prematurely activate the hypothalamic-pituitary-gonadal axis in children, leading to the early appearance of secondary sexual characteristics. Current clinical interventions for this problem must balance the dual goals of "inhibiting excessive hormone secretion" and "ensuring normal growth and development in children," especially avoiding additional burden on children's digestive and metabolic systems. Traditional Chinese medicine, with its advantages of "holistic regulation and syndrome differentiation," has unique potential in regulating endocrine disorders in children; however, its application needs to address issues such as dosage form suitability (e.g., ease of administration for children), drug efficacy stability, and palatability.

[0004] Among existing methods for inhibiting gonadotropins, Western medicine commonly uses GnRH analog injections, which have a relatively fast onset of action. However, these methods have drawbacks, including the need for injection administration, poor compliance in children, and a high incidence of adverse reactions (such as injection site pain and headaches). Traditional Chinese medicine formulas, mostly decoctions, suffer from inconvenience in administration, difficulty in dosage control, and poor stability of active ingredients. Furthermore, some Chinese medicine preparations are not optimized for children's physical characteristics, or their unpleasant taste leads to children's resistance to medication, affecting the continuity of treatment. Summary of the Invention

[0005] Based on this, the purpose of this invention is to provide a herbal formula for inhibiting gonadotropin secretion and its preparation method, so as to solve the technical problem that some traditional Chinese medicine preparations have not been optimized for the physical characteristics of children.

[0006] To achieve the above objectives, the present invention provides the following technical solution: a fragrant tea formula for inhibiting gonadotropin secretion, comprising the following ingredients in parts by weight: 10-15g of vine tea, 5-8g of citron, 5-8g of rehmannia root, 5-8g of anemarrhena rhizome, 5-8g of phellodendron bark, 8-10g of paper mulberry fruit, 8-10g of tangerine seed, 5-8g of turmeric, and 5-8g of jujube.

[0007] The preferred weight proportions of each ingredient are: 12g of vine tea, 6g of citron, 6g of rehmannia root, 6g of anemarrhena rhizome, 5g of phellodendron bark, 9g of paper mulberry fruit, 9g of tangerine seed, 6g of turmeric, and 6g of jujube.

[0008] The phellodendron bark is processed with honey. Take phellodendron bark shreds, add 5%-10% honey water and mix well. Let it soak until the honey water is absorbed. Then, stir-fry over low heat at a temperature not exceeding 60℃ until the surface color deepens and it is no longer sticky. Remove and let cool.

[0009] A method for preparing a fragrant tea formula for stabilizing fertility by inhibiting gonadotropin secretion, comprising the following extraction steps:

[0010] Step 1: Soak the vine tea, citron, and turmeric in 40℃ warm water for 30 minutes, then extract using ultrasound-assisted extraction for 30 minutes. Store the filtrate separately.

[0011] Step 2: Mix the remaining medicinal materials with the dregs from Step 1, add 8 times the amount of boiling water and decoct for 1.5 hours. Combine the filtrate with the filtrate from Step 1.

[0012] The combined filtrate was enriched and purified using continuous countercurrent extraction technology. The extractant used was an ethyl acetate-water biphase system, the extraction temperature was 35±2℃, and the extraction tower speed was 2500 rpm. The light phase rich in flavonoids and saponins was collected for further processing.

[0013] Sodium alginate and chitosan were used as wall materials. After being mixed with the extract at a mass ratio of 1:3, the mixture was sprayed into the calcium chloride solution at a voltage of 15kV using an electrostatic spraying device to form microcapsules with a particle size of 50-100μm. The microcapsules were collected and rinsed with water.

[0014] The microcapsules are mixed with excipients and made into oral instant tablets using direct powder compression technology. The excipients consist of fructooligosaccharides, maltodextrin, and yam powder in a weight ratio of 3:2:1, with fructooligosaccharides accounting for 10% of the total weight of the compressed tablets.

[0015] In summary, the present invention has the following beneficial effects: The formula of the present invention uses nine medicinal materials, including vine tea, citron, and rehmannia root, as raw materials to make traditional Chinese medicine tablets. These tablets ensure that the growth rate of children after treatment remains at a normal level, which is in line with the normal growth rhythm of children of the same age. Furthermore, the tablets are made into oral instant-dissolving tablets, which can be ground and mixed with warm water, milk, or juice for consumption without the need for injection, thus reducing children's fear and resistance caused by injection. Detailed Implementation

[0016] The embodiments of the present invention will now be described.

[0017] The principal herbs in this formula are: Citron (fragrant citron), bitter, sour, and warm in nature, which enters the liver, lung, and spleen meridians. Its function is to soothe the flow of qi and relieve chest congestion. Vine tea (vine tea) is sweet, bland, and cool in nature, entering the liver, lung, and stomach meridians. It clears liver heat and reduces liver fire. Together, these two herbs enter the liver meridian to soothe liver stagnation and clear liver fire. Citron also promotes qi circulation and relieves chest congestion, while vine tea promotes diuresis and eliminates turbidity. Together, they enter the spleen and stomach, regulating the middle jiao to address the root cause of liver fire. The assistant herbs are Rehmannia glutinosa and Broussonetia papyrifera, sweet and cold in nature, entering the liver and kidney meridians. They nourish the true yin of the liver and kidneys to strengthen the foundation. Anemarrhena asphodeloides and Phellodendron chinense are bitter and cold in nature, entering the kidney meridians to purge heat. The four herbs are assistant herbs, enhancing the principal herb's ability to purge the ministerial fire, treating both the symptoms and the root cause. The adjuvant herbs, tangerine seed (bitter and neutral, entering the liver and kidney meridians), soothe liver stagnation, disperse rebellious qi, resolve phlegm, and eliminate breast nodules. Turmeric (bitter, bitter, and cold, entering the liver, heart, and lung meridians), regulates qi, relieves stagnation, and invigorates blood, assisting tangerine seed in clearing phlegm and stagnation. These two herbs assist the principal herb in regulating qi and relieving stagnation, while also targeting early breast development and eliminating nodules. The guiding herb, jujube (sweet and warm, entering the spleen and stomach meridians), tonifies spleen essence and nourishes liver blood, while harmonizing with the other herbs to prevent bitter and cold herbs like anemarrhena and cypress from damaging the spleen, protecting the qi of the middle jiao. The combined use of these herbs addresses liver stagnation, employing both dredging and clearing methods, while adhering to the overall pathogenesis of precocious puberty, combining tonification and purgation to treat both the symptoms and the root cause.

[0018] Example 1

[0019] The herbal formula for the Fragrant Tea Formula is as follows: 10g of vine tea, 5g of citron, 5g of rehmannia root, 5g of anemarrhena rhizome, 5g of phellodendron bark, 8g of paper mulberry fruit, 8g of tangerine seed, 5g of turmeric, and 5g of jujube.

[0020] The herbs in the above-mentioned herbal formula are pre-treated. First, Phellodendron bark is processed. Take 5g of Phellodendron bark shreds, cut them into shreds 2-3mm wide, add them to 5% honey water and stir well. The mass ratio of honey to purified water is 1:1, that is, 0.25g. After mixing well, stir-fry over low heat at 50℃ until the surface color deepens and it is no longer sticky. Remove and let cool. Honey is sweet and neutral in nature, which can significantly alleviate the bitter and cold irritation of Phellodendron bark, and can also strengthen the spleen and harmonize the stomach, thus protecting the spleen and stomach function of children to the greatest extent.

[0021] After the medicinal materials are prepared, the fragrant tea formula for stabilizing growth will then be prepared:

[0022] Step 1: Take vine tea, citron, and turmeric, add 5 times the amount of purified water at 40℃, and soak for 30 minutes; use an ultrasonic extractor to assist extraction for 30 minutes, keeping the temperature of the extract at 40-45℃ during the ultrasonic process to avoid degradation of the active ingredients; after extraction, filter while hot through a 300-mesh filter cloth, and store the filtrate containing volatile oils and water-soluble glycosides at 4℃. Press the residue to recover the residual liquid for later use.

[0023] Step 2: Mix the remaining medicinal materials, namely Rehmannia glutinosa, Anemarrhena asphodeloides, processed Phellodendron chinense, Broussonetia papyrifera, Citrus reticulata seed, and jujube, with the dregs from Step 1. Add 8 times the amount of boiling water and decoct in a clay pot to effectively avoid the influence of metal ions. Maintain a gentle boil for 1.5 hours, stirring once every 20 minutes to ensure that the medicinal materials are heated evenly. After decoction, filter through a 200-mesh filter cloth. Combine the filtrate with the filtrate from Step 1 to obtain a total extract of approximately 300 mL.

[0024] The combined total extract was transferred to a continuous countercurrent extraction tower. An ethyl acetate-water two-phase system was used as the extractant, with a volume ratio of ethyl acetate to water of 1:2. The extraction temperature was controlled at 35±2℃, and the tower rotation speed was adjusted to 2500 rpm for continuous countercurrent extraction for 60 minutes. During the extraction process, the content of flavonoids and saponins in the ethyl acetate phase was monitored by an online detection system. Once the content stabilized, the light phase rich in flavonoids and saponins was collected, and the heavy phase was discarded. The collected light phase was transferred to a rotary evaporator and concentrated to an extract with a relative density of 1.15-1.20 at 45℃ and -0.08 MPa for later use.

[0025] Through the above-mentioned continuous countercurrent contact between two phases, the mass transfer efficiency is much higher than that of batch extraction, which can significantly improve the recovery rate and purity of the target active ingredient.

[0026] Weigh out food-grade sodium alginate and food-grade chitosan, mix them at a mass ratio of 2:1, add purified water to prepare a 2% wall material solution, stir until completely dissolved, and filter through a 0.45μm filter membrane to remove impurities; mix the above concentrated extract with the wall material solution at a mass ratio of 3:1, stir for 30 minutes to form a uniform core-wall mixture; transfer the core-wall mixture into the storage tank of an electrostatic spray device, set the nozzle diameter to 0.2mm, voltage to 15kV, and feed rate to 5mL / h, and spray the mixture into a 3% calcium chloride solution to form microcapsules with a particle size of 50-100μm; collect the microcapsules, rinse them 3 times with purified water, each time using 5 times the mass of the microcapsules, to remove residual calcium chloride on the surface, and place them in a vacuum drying oven to dry until the moisture content is ≤5% for later use.

[0027] By encapsulating active ingredients in natural polymer wall materials, the problems of easy degradation, easy oxidation, and bitter taste of traditional Chinese medicine ingredients are directly solved, and enteric or sustained-release effects can be achieved, improving the bioavailability of the human body.

[0028] Weigh out fructooligosaccharides, maltodextrin, and yam powder, and mix them in a weight ratio of 3:2:1 to prepare an excipient mixture. Mix the dried microcapsules with the excipient mixture, wherein the amount of fructooligosaccharides accounts for 10% of the total weight of the tablets. Place the mixture in a three-dimensional motion mixer and mix for 20 minutes to obtain a uniform tableting material. Transfer the tableting material to a powder direct tableting machine, set the tableting pressure to 5kN and the rotation speed to 10 tablets / minute, and compress it into oral instant tablets with a diameter of 6mm and a thickness of 3mm, each weighing approximately 100mg.

[0029] Because microcapsules have fluidity, compressibility, and stability, they are very suitable for direct tableting, avoiding the damage to microcapsules caused by traditional wet granulation. This improves the decoction into an oral instant tablet, greatly enhancing the convenience and compliance of children taking it.

[0030] Example 2

[0031] This embodiment provides a medicinal formula for a fragrant tea-based fertility treatment: 15g of vine tea, 8g of citron, 8g of rehmannia root, 8g of anemarrhena rhizome, 8g of phellodendron bark, 10g of paper mulberry fruit, 10g of tangerine seed, 8g of turmeric, and 8g of jujube.

[0032] The preparation method of the fragrant tea culture formula in this embodiment is the same as that in Example 1.

[0033] Example 3

[0034] This embodiment provides a medicinal formula for a fragrant tea-based fertility treatment: 12g of vine tea, 6g of citron, 6g of rehmannia root, 6g of anemarrhena rhizome, 5g of phellodendron bark, 9g of paper mulberry fruit, 9g of tangerine seed, 6g of turmeric, and 6g of jujube.

[0035] The preparation method of the fragrant tea culture formula in this embodiment is the same as that in Example 1.

[0036] The following clinical data illustrates the therapeutic effect of the compressed tablets made from the fragrant tea fertility-stabilizing formula of this invention. Specific details are as follows:

[0037] Case 1

[0038] A 6-year-2-month-old girl presented with bilateral breast enlargement for 3 months.

[0039] Chief complaint: The parents found lumps in both of the child's breasts, accompanied by mild tenderness, no vaginal bleeding, and the child's height growth was faster than before.

[0040] Present illness: The child has no special dietary history or history of central nervous system disease; breast development has occurred in the past 3 months, occasional irritability, and normal sleep and appetite.

[0041] Physical examination: Height 122cm, weight 22kg; bilateral breasts stage B2, with mammary buds approximately 1.5cm in diameter, no pubic or axillary hair development; vulva is of childlike type, with no discharge.

[0042] Auxiliary examinations: Bone age X-ray showed a bone age of 7 years and 6 months, which is 14 months ahead of the actual age; sex hormone six-item test: luteinizing hormone 5.8 IU / L, follicle-stimulating hormone 4.2 IU / L, estradiol 38 pg / mL; pelvic ultrasound: uterus size 2.8cm × 1.5cm × 1.2cm, bilateral ovarian volume 2.3mL.

[0043] Medication regimen: Based on the child's weight of 22kg, administer 0.5mg / kg twice daily for 12 consecutive weeks.

[0044] After 12 weeks of treatment, the bilateral breast nodules shrank to 0.8 cm, the tenderness disappeared, and there was no new progression of secondary sexual characteristics; LH decreased to 2.3 IU / L, FSH decreased to 2.8 IU / L, and estradiol decreased to 21 pg / mL; bone age increased by 0.3 months; and height increased by 1.2 cm in the past 3 months, returning to the normal rate for children of the same age.

[0045] Case 2

[0046] A 7-year-5-month-old boy presented with enlarged testicles and rapid height growth over the past 4 months.

[0047] Chief complaint: The parents noticed that the child's testicles were larger than those of children of the same age, and that the child's height had increased by 2.5 cm in the past 4 months, with occasional penile erections.

[0048] Present illness: The child was previously healthy with no history of trauma or infection and had a regular diet; in the past 4 months, he developed testicular enlargement, accompanied by increased activity, but no deepening of voice or development of pubic hair.

[0049] Physical examination: Height 128cm, weight 25kg; testicular volume 6mL / side, penile length 3.2cm, no pubic or axillary hair.

[0050] Auxiliary examinations: Bone age X-ray showed a bone age of 9 years and 1 month; sex hormone panel: LH 6.5 IU / L, FSH 4.8 IU / L, testosterone 156 ng / dL; testicular ultrasound: bilateral testicular parenchyma showed uniform echogenicity and normal blood flow.

[0051] Based on the child's weight of 25kg, administer 0.5mg / kg twice daily for 12 consecutive weeks.

[0052] After 12 weeks of treatment, testicular volume decreased to 4.2 mL / side, and the number of nocturnal penile erections decreased to 1-2 times per month; LH decreased to 2.1 IU / L, FSH decreased to 2.5 IU / L, and testosterone decreased to 98 ng / dL; bone age increased by 0.2 months; and height increased by 1.0 cm in the past 3 months.

[0053] Case 3

[0054] A 5-year-8-month-old girl presented with breast development and vaginal discharge for one month.

[0055] Chief complaint: The parents noticed that the child's breasts were swollen on both sides, and there was a small amount of white vaginal discharge in the past month. There was no vaginal bleeding, and the child's height increased by 0.9 cm in the past month.

[0056] Present illness: The child had taken traditional Chinese medicine for "recurrent respiratory infections" for 2 months. One month after stopping the medication, the child developed breast development. There were no central nervous system symptoms such as headache or vomiting. The child's diet and sleep were normal.

[0057] Physical examination: Height 118cm, weight 20kg; bilateral breasts B2 stage, pubic hair Tanner I stage, vulva clean with a small amount of white discharge, microscopic examination unremarkable.

[0058] Auxiliary examinations: Bone age X-ray showed a bone age of 6 years and 10 months; sex hormone panel: LH 5.2 IU / L, FSH 3.9 IU / L, estradiol 35 pg / mL; pelvic ultrasound: uterus size 2.6cm × 1.4cm × 1.1cm, bilateral ovarian volume 2.1mL.

[0059] Based on the child's weight of 20kg, administer 0.5mg / kg twice daily for 12 consecutive weeks.

[0060] After 12 weeks of treatment, the breast nodules shrank to 0.5 cm, and vaginal discharge disappeared; LH decreased to 1.8 IU / L, FSH decreased to 2.2 IU / L, and estradiol decreased to 18 pg / mL; bone age increased by 0.1 month; and height increased by 1.1 cm in the past 3 months.

[0061] Case 4

[0062] A boy, 8 years and 1 month old, presented with enlarged testicles and the first appearance of pubic hair 3 months prior.

[0063] Chief complaint: The parents noticed that the child's testicles were enlarged, pubic hair appeared in the past 3 months, the child's height increased by 2.3 cm, and the voice became slightly deeper.

[0064] Present illness: The child has no history of specific diseases or hormone exposure; secondary sexual characteristics have progressed rapidly in the past 3 months, accompanied by mood fluctuations and decreased sleep quality.

[0065] Physical examination: Height 132cm, weight 28kg; testicular volume 8mL / side, penile length 3.5cm.

[0066] Auxiliary examinations: Bone age X-ray showed a bone age of 10 years and 3 months; sex hormone panel: LH 7.2 IU / L, FSH 5.5 IU / L, testosterone 182 ng / dL; testicular ultrasound: abundant blood flow in both testes, with normal parenchymal echogenicity.

[0067] The treatment plan for pediatric CPP, namely gonadotropin-releasing hormone agonist therapy, is as follows:

[0068] Triptorelin injection was selected, with an initial dose of 0.1 mg / kg (2.8 mg) administered subcutaneously, followed by injections every 4 weeks at a dose of 0.08 mg / kg, for a total of 12 weeks.

[0069] After 12 weeks of treatment, the testicular volume decreased to 5.5 mL / side, pubic hair did not increase further, and the trend of voice deepening was relieved; LH decreased to 1.5 IU / L, FSH decreased to 2.0 IU / L, and testosterone decreased to 75 ng / dL; bone age increased by 0.1 months; and height increased by 0.8 cm in the past 3 months.

[0070] Analysis of the above cases showed that GnRH-a has a stronger inhibitory effect on gonadotropins, but the LH inhibition rate in cases 1-3 has reached more than 60%, which can meet the clinical needs for inhibitory development and avoid excessive inhibition leading to developmental delays in children.

[0071] In this embodiment, the growth rate of children treated with Xiangcha Wenyufang tablets remained at 1.0-1.2 cm / 3 months, which is in line with the normal growth rhythm of children of the same age; while the growth rate after GnRH-a treatment dropped to 0.8 cm / 3 months, which is slightly lower than the normal range, and long-term use may increase the risk of growth retardation.

[0072] This fragrant tea formula can be made into oral instant tablets, which can be ground and mixed with warm water, milk or juice for consumption. No injection is required, which can reduce children's fear and resistance caused by injection. GnRH-a needs to be injected subcutaneously once every 4 weeks. Repeated injections can easily lead to psychological resistance in children and low compliance with long-term treatment.

[0073] The Phellodendron bark in the Fragrant Tea Formula is processed with honey, which reduces its bitter and cold irritation. The excipients are mild ingredients such as fructooligosaccharides and maltodextrin, which are less irritating to children's gastrointestinal tract. In contrast, GnRH-a, as a hormonal drug, may cause adverse reactions such as hot flashes, vaginal bleeding in girls, and mood swings with long-term use. Therefore, this Fragrant Tea Formula has greater advantages.

[0074] Although embodiments of the invention have been shown and described, these specific embodiments are merely illustrative of the invention and are not intended to limit it. The specific features, structures, materials or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

Claims

1. A kind of inhibiting gonadotropin secretion's Xiangcha stable maintenance formula, it is characterized in that, The raw materials are composed of the following weight parts: Ruscus aculeatus 10-15 g, Citrus aurantium 5-8 g, Rehmannia glutinosa 5-8 g, Anemarrhena asphodeloides 5-8 g, Phellodendron amurense 5-8 g, Fructus Malli 8-10 g, Aurantii Fructus Immaturus 8-10 g, Curcuma 5-8 g, and Jujube 5-8 g.

2. The Xiangcha steady recipe for inhibiting the secretion of gonadotropin according to claim 1, characterized in that: The weight parts of the raw materials are as follows: Ruscus aculeatus 12 g, Citrus aurantium 6 g, Rehmannia glutinosa 6 g, Anemarrhena asphodeloides 6 g, Phellodendron amurense 5 g, Fructus Malli 9 g, Aurantii Fructus Immaturus 9 g, Curcuma 6 g, and Jujube 6 g.

3. The fragrant tea formula for stabilizing fertility by inhibiting gonadotropin secretion according to claim 1, characterized in that: The Phellodendron amurense is prepared by honeying, i.e. Phellodendron amurense silk is mixed with 5% honey water, and then soaked until the honey water is absorbed, and then fried at 50°C until the surface color is darkened and the product is not sticky to the hand.

4. The preparation method of the Xiangcha stable preparation for inhibiting the secretion of gonadotropin according to any one of claims 1-3, characterized in that: The extraction steps are as follows: Step one: Ruscus aculeatus, Citrus aurantium, and Curcuma are soaked in 40°C water for 30 minutes, and then extracted for 30 minutes with ultrasonic assistance, and the filtrate is separately stored; Step two: the remaining medicinal materials are mixed with the residue of step one, and then boiled with 8 times the amount of boiling water for 1.5 hours, and the filtrate is combined with the filtrate of step one.

5. The preparation method of the Cangcha Ranghua stabilizing recipe for inhibiting the secretion of gonadotropin according to claim 4, characterized in that: The combined filtrate is enriched and purified by continuous countercurrent extraction technology, the extraction agent is an ethyl acetate-water two-phase system, the extraction temperature is 35±2°C, and the extraction tower rotation speed is 2500 rpm; the light phase rich in flavonoids and saponins is collected for subsequent processing.

6. The preparation method of the Cangcha Ranghua Decoction for inhibiting the secretion of gonadotropin according to claim 5, characterized in that: The extraction liquid is mixed with sodium alginate and chitosan as wall materials at a mass ratio of 1:3, and then sprayed into a calcium chloride solution at a voltage of 15 kV by an electrostatic spraying device to form microcapsules with a particle size of 50-100 μm, which are then collected and washed with water.

7. The preparation method of the Xiangcha stable preparation for inhibiting the secretion of gonadotropin according to claim 6, characterized in that: The microcapsules are mixed with excipients to form oral dissolving tablets by powder direct compression technology, and the excipients are composed of fructooligosaccharides, malt dextrin, and yam powder at a weight ratio of 3:2:1, wherein the fructooligosaccharides account for 10% of the total weight of the tablets.