TWI642428B - A use of (2r,4r)-1,2,4-trihydroxyheptadec-16-yne in producing a pharmaceutical composition to prevent or treat liver damage - Google Patents

Abstract

The present invention provides a use of the preparation of a pharmaceutical composition comprising (2R,4R)-1,2,4-trihydroxyheptadeca-16-alkyne as an active ingredient for the prevention or treatment of liver damage.

Description

 Application of (2R,4R)-1,2,4-trihydroxyheptadeca-16-alkyne in preparing pharmaceutical composition for preventing or treating liver injury  

The present invention provides a use of the preparation of a pharmaceutical composition comprising (2R,4R)-1,2,4-trihydroxyheptadeca-16-alkyne as an active ingredient for the prevention or treatment of liver damage.

Liver disease is a national disease in Taiwan, which includes alcoholic hepatitis, chemical hepatitis, drug-induced liver disease, fatty liver, viral hepatitis, hereditary liver disease, etc., liver cell damage caused by acute or chronic inflammation caused by these liver diseases. Long-term will likely cause cirrhosis and even liver cancer. Although there is currently no uniform definition of liver injury, any abnormal cause of liver function indicators suggests the presence of liver damage. After liver injury, hepatocytes will be degenerated, necrotic, and fibrous tissue hyperplasia will change the normal liver tissue, which will lead to a series of pathological changes and secondary diseases, so the early diagnosis and maintenance treatment of liver injury will prevent its further development. It is important to restore liver function to normal. At present, there are many choices of liver health foods on the market, but there is no significant liver food health food that is effective and at the same time price.

The present invention discloses the effect of a compound (2R,4R)-1,2,4-trihydroxyheptadeca-16-alkyne on preventing or treating liver damage.

The present invention provides a use of the preparation of a pharmaceutical composition comprising (2R,4R)-1,2,4-trihydroxyheptadeca-16-alkyne as an active ingredient for the prevention or treatment of liver damage.

The liver injury according to the present invention comprises acute and chronic liver damage including, but not limited to, chemical hepatitis, alcoholic hepatitis, fatty acid liver disease, hepatitis virus or non-hepatitis virus infection, immune dysfunction, liver fibrosis, or liver cancer. Caused by.

In the chemical hepatitis according to the present invention, the inducing substances include, but are not limited to, halogen-containing organic compounds such as ethylene dichloride, carbon tetrachloride, propylene dichloride, and the like. Carbon tetrabromide, tetrachloroethane (1,1,2,2-tetrachloroethane), acetylene tetrabromide, ethylene dibromide, etc.; naphthalene (naphthalene) Chlorinated naphthalenes such as trichloronaphthalene, tetrachloronaphthalene, pentachloronaphthalene, octachloronaphthalene, etc.; guanamine compounds such as dimethyl formamide, dimethyl acetamide, etc.; Nitramine compounds such as N-nitrosodimethylamine; furan compounds such as tetrahydrofuran; aliphatic nitrogen compounds such as 2-nitropropane; aromatic amines a compound such as 4,4'-diaminodiphenylmethane or the like; an aliphatic amine-containing compound such as trinitrotoluene (2,4,6-trinitrotoluene) or the like; a metal element or a compound Such as arsenic, beryllium, and thallium ), copper (copper), selenium (Selenium) and other elements and their compounds, or chromic acid or chromium (chromate); insecticides, weeding or fumigants and other pesticides such as DDT and other organic compounds containing chlorine or other halogens a compound used as a pesticide such as a bipyridine compound such as barragalin, a nitrophenol or a chlorophenol; an ethylene compound such as vinyl chloride, vinylidene chloride, or vinyl toluene. Etc.; and other such as diphenyl, polychlorinated biphenyl (PCB), allyl alcohol, chlorine, phosphorus, ethylene oxide, and the like.

The use of the pharmaceutical composition of the present invention for the treatment of fatty acid liver disease, including but not limited to non-alcoholic fatty acid liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), fatty liver disease caused by hepatitis Fatty liver disease caused by obesity, fatty liver disease caused by diabetes, fatty liver disease caused by insulin resistance, fatty liver disease caused by hypertriglyceridemia, no beta lipoproteinemia, glycogen storage disease, Weber- Chris Shin disease, Wolman's disease, acute fatty liver in pregnancy and lipid malnutrition.

Aspartate transaminase (GOT/AST) and alanine transaminase (GPT/ALT) in serum are commonly used as indicators for detecting liver damage. In several embodiments of the invention, (2R,4R)-1,2,4-trihydroxyheptadeca-16-alkyne reduces elevated liver function indicators induced by carbon tetrachloride, alcohol, or a high-fat diet, The liver function indicator comprises aspartate transaminase and alanine transaminase.

In one embodiment, (2R,4R)-1,2,4-trihydroxyheptadeca-16-alkyne is administered to an individual using liver damage induced by carbon tetrachloride, and the result is (2R, 4R)- 1,2,4-trihydroxyheptadeca-16-alkyne is effective in the treatment of hepatocellular damage and tissue abnormalities caused by chemical hepatitis.

In one embodiment, (2R,4R)-1,2,4-trihydroxyheptadeca-16-alkyne is administered to an individual suffering from alcohol (ethanol)-induced liver damage, and the result is (2R, 4R)-1 2,4-trihydroxyheptadeca-16-alkyne is effective in the treatment of hepatocyte injury and tissue abnormalities caused by alcoholic hepatitis.

In one embodiment, (2R,4R)-1,2,4-trihydroxyheptadeca-16-alkyne is administered to an individual with a liver injury induced by a high-fat diet, and the result is (2R, 4R)-1, 2,4-trihydroxyheptadeca-16-alkyne effectively treats hepatocyte damage and tissue abnormalities caused by fatty acid liver disease.

The composition of the present invention may be in the form of a solid, a solution, an emulsion, a dispersion, a micelle, a liposome, and other composition products containing, as an active ingredient, one or more of the ingredients of the present invention, or with an organic or inorganic carrier or The excipients are mixed for application to enteral or parenteral administration. The active ingredient may be mixed, for example, in a pharmaceutically acceptable usually non-toxic vehicle such as a tablet, pill, capsule, suppository, solution, emulsion, suspension, and any other suitable form for use. Carriers which may be used include glucose, lactose, gum arabic, gelatin, mannitol, starch paste, magnesium tricaprate, talc, corn starch, keratin, colloidal cerium oxide, potato starch, urea, medium chain length triglycerides. , dextran, and other carriers suitable for the preparation of the formulation, solid, semi-solid or liquid form. In addition, stabilizers, thickeners and colorants and perfumes may also be used as an aid.

The compositions of the present invention may be administered orally, for example, as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs. Compositions for oral use can be prepared according to various known pharmaceutical composition preparation methods, and the compositions may contain one or more sweeteners such as sucrose, lactose or saccharin, such as mint, wintergreen or cherry. Colorants and preservatives provide pharmaceutical aesthetics and mouthfeel. Tablets mixed with the active ingredient and a pharmaceutically acceptable non-toxic excipient can also be produced by known methods. Excipients which may be used are, for example, (1) inert diluents such as calcium carbonate, lactose, calcium phosphate or sodium phosphate; (2) granulating agents and disintegrating agents such as corn starch, potato starch or alginic acid; Adhesives such as tragacanth, corn starch, gelatin or gum arabic, and (4) lubricants such as magnesium stearate, stearic acid or talc. The tablets may be uncoated or may be coated by known techniques to delay disintegration and absorption in the gastrointestinal tract, thereby providing a sustained action over a longer period of time. For example, a time delay material such as glyceryl monostearate or glyceryl distearate may be employed, or may be coated by techniques such as those described in U.S. Patent Nos. 4,256,108; 4,160,452; and 4,265,874, to produce controlled release. Osmotic treatment tablets.

In some cases, the compositions for oral use can be in the form of hard gelatin capsules in which the active ingredient is mixed with an inert solid diluent such as calcium carbonate, calcium phosphate or kaolin. They may also be in the form of soft gelatin capsules in which the active ingredient is mixed with water or oil medium, such as peanut oil, liquid paraffin or olive oil.

Embodiments of the compositions of the invention may also be in the form of a sterile injectable suspension. This suspension may be formulated according to known methods using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Sterile, fixed oils are usually employed as a solvent or suspension medium. For this purpose, any mild fixed oil can be used, including synthetic mono- or diglycerides, fatty acids (including oleic acid), naturally occurring vegetable oils such as sesame oil, coconut oil, peanut oil, cottonseed oil, etc., or synthetic fatty acid carriers. Such as ethyl oleate or the like. Buffering agents, preservatives, antioxidants, and the like can be combined as needed.

Embodiments of the compositions of the invention may also be administered in the form of a suppository in the rectal cavity. By combining the drug with a suitable non-irritating excipient, such as a synthetic glyceride of cocoa butter or polyethylene glycol, the composition is solid at room temperature but liquefied and/or dissolved in the rectal cavity. To release the drug.

Since individual subjects may exhibit broad variations in the severity of the symptoms, and each drug has its own unique therapeutic profile, the composition of the present invention should be performed by the physician to determine the subject's response to the treatment and to vary the dosage accordingly. .

Figure 1. TY reduces abnormal liver function index caused by carbon tetrachloride. (A) GOT/AST and (B) GPT/ALT in serum of rats with acute hepatic inflammation were tested by carbon tetrachloride. Three male Wistar rats were included in each experiment.

Figure 2. TY reduces liver cell damage and necrosis caused by carbon tetrachloride. The tissue pattern of the liver of rats with acute hepatic inflammation caused by carbon tetrachloride was observed by H&E staining. Each group consisted of three male Wistar rats.

Figure 3. TY reduces abnormal liver function index caused by ethanol. (A) GOT/AST and (B) GPT/ALT in serum of rats with acute hepatic inflammation were tested by ethanol, and three male Wistar rats were included in each experiment.

Figure 4. TY reduces liver cell damage and abnormalities caused by ethanol. The tissue pattern of the liver of rats with acute hepatic inflammation caused by ethanol was observed by H&E staining. Each group consisted of three male Wistar rats.

Figure 5. TY reduces liver dysfunction caused by fatty acid liver disease induced by high fat diet. (A) GOT/AST and (B) GPT/ALT in serum of chronic liver-inflamed mice caused by high-fat diet, and 4-5 male B6 mice were included in each experiment.

Figure 6. TY reduces the triglyceride content in the serum of mice with fatty liver disease induced by high fat diet. The serum triglyceride content in the serum of mice with chronic liver inflammation caused by high fat diet was tested. Each group included 4-5 male B6 mice.

Figure 7. TY treatment of liver cell damage and abnormalities induced by fatty fat liver disease induced by high fat diet. The tissue pattern of the liver of mice with chronic liver inflammation caused by high fat diet was observed by H&E staining. Each group of experiments contained 4-5 male B6 mice.

The singular forms "a", "the" and "the" For example, reference to "a derivative" includes a plurality of such derivatives, and the reference to "a" includes reference to one or more individual.

Also, the use of "or" means "and/or" unless otherwise stated. Similarly, "including" and "including" are used interchangeably and are not intended to be limiting.

It will be further understood that when the description of the various embodiments uses the term "comprising", it will be understood by those skilled in the art that in certain specific circumstances, the language may be "consisting essentially of" or "by." ..... composition" to describe the embodiment.

All technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present disclosure pertains, unless otherwise defined. Although methods and materials similar or equivalent to those described herein can be used in the practice of the methods and compositions disclosed, only exemplary methods, devices, and materials are described herein.

The disclosures discussed above and throughout the article are provided solely for disclosure prior to the filing date of this application. Nothing herein is to be construed as an admission that the invention

The present invention provides a use of a pharmaceutical composition comprising (2R,4R)-1,2,4-trihydroxyheptadeca-16-alkyne as an active ingredient for the preparation or prevention of liver damage.

The preparation method of (2R, 4R)-1,2,4-trihydroxyheptadeca-16-yne in the present disclosure can be referred to the Chinese Mingguo invention patent publication TW201636039A. About 11.9 kg of immature avocado fruit was sliced and dried in an oven at 50 ° C to obtain a dried avocado sample weighing about 2.3 kg. The dried avocado sample was extracted with methanol at room temperature and the extraction step was repeated three times to obtain a higher purity methanol extract. The ethyl acetate extract (EtOAc: H ₂ O 1:1) was added to separate the methanol extract to ethyl acetate-soluble fraction (EtOAc-soluble fraction) and water-soluble fraction. (H ₂ O-soluble fraction). Approximately 100 grams of the ethyl acetate-soluble fraction was added to a column packed with cerium oxide colloid (70-230, Merck) for chromatography and purification. After elution with a concentration gradient elution of n-hexane-ethyl acetate (n-hexane-EtOAc), 12 fractions (A-1 to A-12) were obtained. Next, 10.5 g of the A-12 separation liquid was recrystallized using n-hexane to obtain crystals (A-12-C) and mother liquor (A-12-M). Next, 10 g of A-12-M was chromatographed on a column packed with ruthenium dioxide colloid (230-400 mesh, Merck), and eluted with a concentration gradient elution solution of n-hexane-ethyl acetate to obtain 7 A sub-picture (A-12-M-1~A-12-M-7). Next, 7.3 g of A-12-M-4 was chromatographed on a RP-C18 column (spherical C 18 100A reversed-phase silica gel (RP-18), 20-40 μM, Silicycle), and acetone-water was used. (1:1) elution, by nuclear magnetic resonance (NMR) analysis and comparison, about 113 mg of (2 R , 4 R )-1,2,4-trihydroxyheptadecane- 16-Alkyne, as shown in formula (I).

For convenience of explanation, in the following description, TY is abbreviated as (2R, 4R)-1,2,4-trihydroxyheptadeca-16-alkyne.

The following examples are not intended to be limiting, but merely to present various aspects of the invention.

Example 1. Test TY for the treatment of acute hepatic inflammation caused by carbon tetrachloride. Nine male Wistar rats (200-250 g) were randomly divided into 3 groups, 3 Wistar rats in each group, respectively 1. Healthy control group: the same volume of drug solvent and intraperitoneal injection of olive oil (2.5) Mg/kg). 2. Negative control group (carbon tetrachloride and physiological saline): the same volume of physiological saline as TY and 20% carbon tetrachloride/olive oil were intraperitoneally injected. 3. Experimental group (carbon tetrachloride and TY 100 mg / kg / day): TY 100 mg / kg / day and intraperitoneal injection of 20% carbon tetrachloride / olive oil. First, fill the drug solvent or TY once a day. The first feeding was defined as Day 1, and 1 hour after the fourth day of irrigation, the first group was given intraperitoneal injection of olive oil (2.5 mg/kg), and the third group was given intraperitoneal injection of 20%. Carbon chloride/olive oil (2.5 mg/kg) must be fasted 12 hours after injection, and all Wistar rats are sacrificed 12 hours after fasting. Before sacrifice, the blood is taken from the heart and the serum is separated for analysis of the biochemical function of the liver. Figures 1A and 1B show that carbon tetrachloride significantly improves the liver function index GOT/AST and GPT/ALT of Wistar rats, while TY can significantly reduce the liver function index GOT/AST and GPI/ALT of carbon tetrachloride. This result represents that TY has abnormal liver function caused by the treatment of carbon tetrachloride.

Example 2 TY treatment of liver cell damage necrosis caused by carbon tetrachloride. Nine male Wistar rats (200-250 g) were randomly divided into 3 groups, 3 Wistar rats in each group, respectively 1. Healthy control group: the same volume of drug solvent and intraperitoneal injection of olive oil (2.5) Mg/kg). 2. Negative control group (carbon tetrachloride and physiological saline): the same volume of physiological saline as TY and 20% carbon tetrachloride/olive oil were intraperitoneally injected. 3. Experimental group (carbon tetrachloride and TY 100 mg / kg / day): TY 100 mg / kg / day and intraperitoneal injection of 20% carbon tetrachloride / olive oil. First, daily intake of physiological saline or TY 1 time, the first feeding is defined as the first day, 1 hour after the fourth day of feeding, the first group is given intraperitoneal injection of olive oil (2.5 mg / kg), the first 2-3 groups were given a 20% carbon tetrachloride/olive oil (2.5 mg/kg) in the abdominal cavity. Fasting was required 12 hours after the injection. Wistar rats were sacrificed 12 hours after fasting. After sacrificed the rats, the liver was collected and soaked with formalin, then stained with H&E stain, and then observed and photographed by microscope. Figure 2 shows that rats injected with carbon tetrachloride caused significant liver damage (compared to healthy controls), H&E staining showed hepatocyte necrosis near the central vein and overall tissue disorder, while TY was able to effectively reduce carbon tetrachloride Hepatocyte necrosis near the central vein.

Example 3: Test TY for the treatment of acute liver inflammation caused by alcohol (ethanol). Nine male Wistar rats (200-250 g) were divided into 3 groups, 3 Wistar rats in each group, respectively 1. Healthy control group: the same volume of physiological saline (2.5 mg/kg) was administered. 2. Negative control group (ethanol and physiological saline): TY is the physiological saline solution of the same body and is fed with 50% ethanol. 3. Experimental group (ethanol and TY 100 mg / kg / day): TY 100 mg / kg / day and 50% ethanol. First, the drug solvent or TY was administered once a day. The first feeding was defined as the first day, and the first group was administered with the physiological saline (2.5 mg/kg) one hour after the fourth day of irrigation. Groups 2-3 were given 50% ethanol (2.5 mg/kg) for feeding, and ethanol was administered for 12 hours after the first feeding. Fasting for 12 hours after the second feeding, fasting After the 12 hours, all Wistar rats were sacrificed. Before sacrifice, the blood is taken from the heart and the serum is separated for analysis of the biochemical function of the liver. Figures 3A and 3B show that ethanol significantly increased the liver function index GOT/AST and GPT/ALT in Wistar rats, while TY significantly reduced the liver function index GOT/AST and GPT/ALT in ethanol. This result represents that TY has abnormal liver function caused by treatment of ethanol.

Example 4: TY treatment of liver cell damage and abnormalities caused by alcohol (ethanol). Nine male Wistar rats (200-250 g) were randomly divided into 3 groups, 3 Wistar rats in each group, respectively 1. Healthy control group: the same volume of drug solvent as TY and the physiological saline solution ( 2.5 mg / kg). 2. Negative control group (ethanol and physiological saline): Physic saline in the same body as 舆TY and 50% ethanol. 3. Experimental group (ethanol and TY 100 mg / kg / day): TY 100 mg / kg / day and 50% ethanol. First, the food solvent or TY was filled once a day. The first feeding was defined as the first day, and the first group was given 1 hour after the feeding. The first group was given the physiological saline (2.5 mg/kg). The three groups were given 50% ethanol (2.5 mg/kg) by injection, and then ethanol was administered 12 hours after the first feeding. Fasting was necessary 12 hours after the second feeding, 12 hours after fasting. Sacrifice all Wistar rats. After sacrificed the rats, the liver was collected and soaked with formalin, then stained with H&E stain, and then observed and photographed by microscope. Figure 4 shows that rats fed with ethanol caused significant liver damage and tissue abnormalities (white highlights in the blue circle compared with healthy controls), H&E staining showed hepatocyte damage and overall tissue disorder, while TY was able to effectively reduce ethanol Caused by liver damage and tissue abnormalities.

Example 5: Effect of TY on the treatment of chronic hepatitis caused by fatty acid liver disease by high fat diet. Fifteen male 8-10 week old C57BL/6 ( B6 ) mice (20-22 g) were randomly divided into 3 groups, 4-5 B6 mice in each group, respectively 1. Healthy control group: normal feed intake (% fat fat percentage 5-6%); 2. Negative control group: high fat diet (60% fat fat percentage) and normal saline; 3. Experimental group: animals were given the same high fat as the negative control group The feed is processed and fed TY 100 mg / kg / day. The experimental samples were administered daily starting 1 week before the high fat diet induced liver injury. The first group and the second group were fed with the same volume of drug solvent as TY, and the third group was fed with TY 100 mg/kg daily. After one week, the second group and the third group began to give high-fat diet, and continued to feed TY with the same volume of drug solvent and TY 100 mg / kg / day for 18 weeks, the mice were administered at the 18th week. Fasted, sacrificed all B6 mice 12 hours after fasting. Before sacrifice, the blood is taken from the heart and the serum is separated for analysis of the biochemical function of the liver. Figures 5A and 5B show that high-fat diet significantly increased liver function index GOT/AST and GPT/ALT in B6 mice, while TY significantly reduced liver function index GOT/AST and GPT/ALT from high-fat diet. This result represents that TY has a liver function abnormality caused by the treatment of fatty liver disease induced by high fat diet.

Example 6. TY reduces the triglyceride content in the serum of mice with fatty liver disease induced by high fat diet. Fifteen male 8-10 week old C57BL/6 (B6) mice (20-22 g) were randomly divided into 3 groups, 4-5 B6 mice in each group, respectively 1. Healthy control group: normal feed intake (% fat fat percentage 5-6%); 2. Negative control group: intake of high-fat diet (60% of fat calories) and feeding of physiological saline (high-fat diet and physiological saline); 3. Experimental group: animal-administered Treat with the same high-fat diet as the negative control group and feed TY 100 mg/kg/day (high-fat diet with TY). The experimental samples were administered daily starting 1 week before the high fat diet induced liver injury. The first group and the second group were fed with the same volume of drug solvent as TY, and the third group was fed with TY 100 mg/kg daily. After one week, the second group and the third group began to give high-fat diet, and continued to feed TY with the same volume of drug solvent and TY100 mg/kg/day for 18 weeks, and the mice were administered at the 18th week. Fasting, sacrificed all B6 mice 12 hours after fasting. Before sacrifice, blood was taken from the heart and serum was separated for analysis of the triglyceride content in the serum. Figure 6 shows that the high-fat diet significantly increased the triglyceride content in the serum of B6 mice, while TY significantly reduced the triglyceride content in the serum elevated by the high-fat diet. This result represents that TY has a lower triglyceride content in the serum of mice fed with fatty liver disease induced by high fat diet.

Example 7 TY treatment of liver cell damage and abnormality induced by fatty fat liver disease by high fat diet. Fifteen male 8-10 week old C57BL/6 (B6) mice (20-22 g) were divided into 3 groups, 4-5 B6 mice in each group, respectively 1. Healthy control group: normal feed intake (% fat fat percentage 5-6%); 2. Negative control group: high fat diet (60% fat fat) and normal saline; 3. Experimental group: animals given the same high fat as the negative control group Feed the feed and feed TY 100 mg / kg / day (high fat feed with TY). The experimental samples were given daily starting from 1 week before the high fat diet induced liver injury. The first group and the second group were fed with the same volume of drug solvent per day, and the third group was fed with TY 100 mg/kg daily. After one week, the second group and the third group began to give high-fat diet, and continued to feed TY with the same volume of drug solvent and TY 100 mg / kg / day for 18 weeks, the mice were administered at the 18th week. Fasted, sacrificed all B6 mice 12 hours after fasting. After sacrifice of the mouse, the liver was collected and soaked with formalin, then stained with H&E stain, and then observed and photographed by microscope. Figure 7 shows that mice fed high-fat diets caused significant liver damage and tissue abnormalities (compared to healthy controls). H&E staining showed hepatocyte damage and overall tissue disorder (formation of many vacuoles), while TY was able to effectively reduce high fat. Liver damage and tissue abnormalities caused by feed.

This invention has been described and illustrated in sufficient detail to enable a person of ordinary skill in the art to which this invention pertains. The various modifications, modifications, and improvements should be considered. It is no different from the spirit and scope of this invention.

It is obvious to those skilled in the art that the present invention can readily understand and achieve the objects of the present invention and obtain the results and advantages mentioned. The animals, materials, and processes and methods for producing the same are representative of the preferred embodiments and are exemplary in nature and are not intended to limit the scope of the invention. Modifications or other uses that may occur to those skilled in the art and in the art of making or using the art are encompassed within the spirit of the invention and are defined by the scope of the invention.

Claims (2)

Use of a pharmaceutical composition for the preparation of a medicament for preventing or treating liver damage, wherein the pharmaceutical composition comprises (2R, 4R)-1,2,4-trihydroxyheptadeca-16-yne or its pharmaceutically acceptable Accepted salts, tautomers, stereoisomers or enantiomers are included as active ingredients, wherein the liver damage is caused by chemical hepatitis, alcoholic hepatitis, or fatty acid liver disease. The use of the first aspect of the invention, wherein the method of administration of the medicament is one or a combination of the following groups: tablets, troches, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft Capsules, syrups or elixirs, or injections.