JP4863641B2 - Ointment for dispersal hemorrhoids with excellent usability and high temperature stability - Google Patents

Description

  The present invention relates to a dispersion type hemorrhoid treatment ointment having excellent usability and high temperature stability.

  Vaginal illness is a symptom that occurs in the anus. Since the affected area of the hemorrhoid disease is in the lower part of the body and always faces downward, ointments and suppositories that are easy to stay in the affected area and are easy to apply are widely used as external preparations.

  However, the anal part always takes a directional movement that is closed by the sphincter, is a passage at the time of excretion, and is a sensitive part where the nerves are concentrated. There are problems that drugs are sometimes removed and that they are likely to cause discomfort when administered. These are problems specific to gonorrhea.

  Therefore, in particular, an ointment for treating hemorrhoids is easy to apply and needs to dissolve and diffuse quickly after being administered. Therefore, these ointments are designed to dissolve at body temperature. However, the conventional ointment becomes very unstable at a high temperature, and there is a problem that each component repeats dissolution and solidification before use, resulting in a non-uniform mixture. On the other hand, when trying to ensure uniformity, there is a problem that the feeling of use deteriorates due to the ointment becoming too hard.

  An object of the present invention is to provide an ointment for dispersal hemorrhoids having excellent usability and high temperature stability.

  As a result of intensive research in view of the above problems, the inventors of the present invention can maintain uniformity even in a high-temperature region by using a combination of a drug, white petrolatum, microcrystalline wax, and liquid oil at room temperature, and the usability is also good. The present invention has been completed by discovering that an ointment for treating hemorrhoids can be prepared.

That is, the present invention provides the following items:
Item 1. An ointment for treating dispersal hemorrhoids characterized by comprising a drug, white petrolatum, microcrystalline wax, and oil at room temperature;
Item 2. 2. The ointment for treating dispersal hemorrhoids according to claim 1, comprising 2 to 7% by weight of the microcrystalline wax based on the total amount of the ointment;
Item 3. Item 3. The dispersion type hemorrhoid treatment ointment according to Item 1 or 2, comprising the room temperature liquid oil in an amount of 3 to 20% by weight based on the total amount of the ointment.
Item 4. Item 4. The dispersal hemorrhoid treatment according to any one of Items 1 to 3, wherein the content of the microcrystalline wax and the liquid oil at room temperature is 0.4 to 10 parts by weight with respect to 1 part by weight of the former. Ointment;
Item 5. Item 5. The ointment for treating dispersal hemorrhoids according to any one of Items 1 to 4, comprising the white petrolatum 43 to 93.5% by weight based on the total amount of the ointment;
Item 6. Item 5. The ointment for treating dispersal hemorrhoids according to any one of Items 1 to 5, wherein the agent is contained in an amount of 1.5 to 30% by weight based on the total amount of the ointment;
Item 7. Item 5. The ointment for treating dispersal hemorrhoids according to any one of Items 1 to 6, wherein the white petrolatum has a color concentration of 0.5 to 20Y;
Item 8. Item 8. The dispersion type hemorrhoid treatment ointment according to any one of Items 1 to 7, comprising at least one oil selected from the group consisting of liquid paraffin, squalane and vegetable oil as the room temperature liquid oil. Agent;
Item 9. Item 9. The dispersal hemorrhoid treatment ointment according to Item 8, wherein the vegetable oil is olive oil;
Item 10. Item 10. The ointment for treatment of disseminated hemorrhoids according to any one of Items 1 to 9, comprising a drug selected from the group consisting of an anti-inflammatory agent, a local anesthetic, a refreshing agent, and an astringent. ;
Item 11. Item 11. The dispersal hemorrhoid treatment ointment according to Item 10, wherein the anti-inflammatory agent is a steroidal anti-inflammatory agent;
Item 12. Item 12. The dispersal hemorrhoid treatment ointment according to Item 10 or 11, wherein the astringent is zinc oxide.

  The present invention is described in detail below.

  Agents that can be incorporated into the ointment for treatment of dispersal hemorrhoids of the present invention include, but are not limited to, agents that improve symptoms associated with hemorrhoids such as anti-inflammatory agents, local anesthetics, refreshing agents, and astringents. . These agents can be used alone or in combination of two or more.

  The anti-inflammatory agent may be a steroidal anti-inflammatory agent or a non-steroidal anti-inflammatory agent.

  Steroidal anti-inflammatory agents include dexamethasone, triamcinolone acetonide, beclomethasone propionate, hydrocortisone succinate, methyl succinate, prednisolone, dexamethasone acetate, hydrocortisone acetate, prednisolone acetate, dexamethasone metasulfonate benzoate, triamcinolone diacetate, butylacetate Prednisolone, dexamethasone phosphate, hydrocortisone phosphate, prednisolone phosphate, betamethasone phosphate, prednisolone succinate, cortisone acetate, parameterzone acetate, methylprednisolone acetate, triamcinolone, hydrocortisone, prednisolone, betamethasone valerate, prednisolone tron valerate acetate , Dexamethasone valerate, betamethasone valerate, diflupredonate acetate Diflorazone acetate, difluprednate, betamethasone dipropionate, flumetasone pivalate, fluocinide, fluocinolone acetonide, alcromethasone propionate, beclomethasone propionate, clobetasone butyrate, hydrocortisone butyrate, hydrocortisone butyrate, flurocortisone acetate, flurocortisone acetate Examples include, but are not limited to, dexamethasone and methylprednisolone. Among the steroidal anti-inflammatory agents described above, prednisolone, prednisolone acetate, hydrocortisone, and hydrocortisone acetate are preferable as a therapeutic agent for hemorrhoids. These steroidal anti-inflammatory agents can be used alone or in combination of two or more.

  Non-steroidal anti-inflammatory agents include indomethacin, ibuprofen, ibuprofen piconol, ufenamate, glycyrrhetinic acid, crotamiton, spirophene, glycyrrhizic acid, diclofenac sodium, sulindac, flurbiprofen, salts or derivatives thereof, etc. It is not limited to these. These non-steroidal anti-inflammatory agents can be used alone or in combination of two or more.

  Examples of the local anesthetic include, but are not limited to, lidocaine, procaine, ethyl aminobenzoate, dibucaine, mepivacaine, salts or derivatives thereof, and the like. These local anesthetics can be used alone or in combination of two or more.

  Examples of astringents include, but are not limited to, zinc oxide, tannic acid, aluminum sulfate, aluminum potassium sulfate, zinc sulfide, azulene, calamine, lead acetate, bismuth subnitrate, and the like. Preferred astringents in the present invention include zinc oxide and tannic acid. These astringents can be used alone or in combination of two or more.

  As a refreshing agent, menthol (l-menthol, dl-menthol), camphor (dl-camphor, d-camphor), borneol (d-borneol, rhubarb), geraniol, cineol, linalool, limonene, menthone, Carvone, anethole, methyl salicylate, cinnamic aldehyde, octyl aldehyde, linalyl acetate, menthyl acetate, pinene, lactyl menthyl, eucalyptus oil, bergamot oil, fennel oil, rose oil, peppermint oil, peppermint oil, spearmint oil, dipterocarpaceae Essential oil, rosmarin oil, lavender oil, mastic oil, parsley oil, anise oil, eucalyptus oil, wintergreen oil, cassia oil, lemon oil, orange oil, cardamom oil, coriander oil, mandarin oil, lime oil, lore Oil, chamomile oil, caraway oil, bay oil, lemon grass oil, pine needle oil, neroli oil, and jasmine oil, and the like, without limitation. These refreshing agents can be used alone or in combination of two or more.

  As white petrolatum which can be blended in the dispersion type hemorrhoid treatment ointment of the present invention, those having a color strength of about 0.5Y to 20Y can be used, but are not limited thereto. The white petrolatum that can be blended in the dispersion type hemorrhoid treatment ointment of the present invention has a color strength of preferably about 1.3Y to 20Y, more preferably about 1.8 to 20Y. These white petrolatum can be used individually by 1 type or in mixture of 2 or more types.

  The room temperature liquid oil that can be blended in the dispersion type hemorrhoid treatment ointment of the present invention may be any oil that is liquid at a temperature of about 25 ° C.

  Examples of such room temperature liquid oils include, but are not limited to, hydrocarbons and vegetable oils. These room temperature liquid oils can be used singly or in combination of two or more.

  Examples of hydrocarbons include, but are not limited to, liquid paraffin, liquid isoparaffin, light liquid paraffin, light liquid isoparaffin, squalene, squalane, pristane, and the like. Among the above-described hydrocarbons, liquid paraffin, light liquid paraffin, squalene and squalane are preferred for use as a therapeutic agent for hemorrhoids. These hydrocarbons can be used individually by 1 type or in mixture of 2 or more types.

  Examples of vegetable oils include, but are not limited to, olive oil, soybean oil, peanut oil, safflower oil, nuka oil, sesame oil, camellia oil, corn oil, menditus oil, coconut oil, and the like. A preferred vegetable oil is olive oil. These vegetable oils can be used singly or in combination of two or more.

  The content of the drug in the dispersion type hemorrhoid treatment ointment of the present invention is usually about 1.5 to 30% by weight, preferably about 5 to 25% by weight, more preferably about 7 to 20% by weight. If the drug content is too high, there will be a safety problem, and if it is too low, the effect as a hemorrhoid treatment drug will be reduced.

  The content of the white petrolatum in the dispersion type hemorrhoid treatment ointment of the present invention is usually about 43 to 93.5% by weight, preferably about 45 to 85% by weight, and more preferably about 60 to 80% by weight. If the content of white petrolatum is too high, the dispersion system for treating hemorrhoids becomes soft, and if it is too low, it becomes hard.

  The content of the microcrystalline wax in the dispersion type hemorrhoid treatment ointment of the present invention is usually about 2 to 7% by weight, preferably about 2 to 6% by weight, and more preferably about 2 to 4% by weight. If the content of the microcrystalline wax is too large, the dispersion type ointment treatment ointment becomes hard, and if it is too small, the stability at high temperatures is deteriorated.

  The content of the room temperature liquid oil in the dispersion type hemorrhoid treatment ointment of the present invention is usually about 3 to 20% by weight, preferably about 9 to 20% by weight, more preferably about 10 to 14% by weight. . If the content of oil at room temperature is too high, the dispersion ointment ointment becomes very sticky, and if it is too low, the elongation becomes worse.

  Further, in the dispersion type hemorrhoid treatment ointment of the present invention, the content ratio of the microcrystalline wax and the room temperature liquid oil is about 0.4 to 10 parts by weight of the latter with respect to 1 part by weight of the former. The amount is preferably about 1.5 to 10 parts by weight, more preferably about 2.5 to 7 parts by weight. By setting the content ratio of the microcrystalline wax and the oil at room temperature to be within the above range, an ointment with better high-temperature stability and usability can be prepared.

  Further, the dispersal hemorrhoid ointment of the present invention is an optional component as long as there is no problem with the feeling of use and stability, tissue activator, fragrance, colorant, warm feeling, thermal component, extracts, surfactant, Solvent, Solubilizer, pH adjuster, Buffer, Base, Unwrapping agent, Emulsifier, Suspension, Softener, Thickener, Dispersant, Excipient, Lubricant, Antioxidant, Preservative, Preservation An appropriate amount of an agent, a plasticizer, and the like may be blended.

  In the dispersion type hemorrhoid treatment ointment of the present invention, the total content of white petrolatum and microcrystalline wax is preferably more than about 50% by weight, more preferably about 60% by weight or more. When the total content is high, the stability of the dispersion type hemorrhoid treatment ointment increases.

  The dispersion type hemorrhoid treatment ointment of the present invention can be prepared by mixing the above-mentioned drug, white petrolatum, microcrystalline wax, and room temperature liquid oil. Conditions such as temperature, order of addition of each component, mixing time, etc. in the preparation are easily selected based on the common general technical knowledge in the field according to the physical or chemical properties of each component, concentration, equipment capability, etc. I can do it. In this case, the separation can be further suppressed by mixing each component while degassing under reduced pressure.

  INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a dispersion type hemorrhoid treatment ointment excellent in both feeling of use and high temperature stability. That is, the dispersion type hemorrhoid treatment ointment of the present invention is excellent in use feeling and has the property that its fluidity increases at a high temperature but solidifies in a uniform state when re-solidified at room temperature.

Preparation Examples Agents such as zinc oxide and lidocaine, white petrolatum, microcrystalline wax (MK wax) and room temperature liquid oils were mixed to prepare a dispersion type hemorrhoid treatment ointment of the present invention (Examples 1 to 16). . Further, a saliva beeswax and carnal barrow were used instead of microcrystalline wax (MK wax) to prepare a dispersion type hemorrhoid treatment ointment, which was used as a comparative example. The composition of the dispersion type hemorrhoid treatment ointment in Examples and Comparative Examples is as shown in Table 1 below.

  Here, white petrolatum 1 to 3 indicate white petrolatum having different purification degrees, and the purification degree uses the color concentration as an index. Table 2 below shows the color concentration and product name of white petrolatum used.

Test Example For each of the examples and comparative examples, a separation test and a sensory test on the feeling of use were performed according to the following procedure.

(1) Separation test (i) About 5 g of each ointment of each example and comparative example is put into a screw tube (24 × 50).

  (Ii) Leave the screw tube at 50 ° C./7 days. During standing, some of each ointment separates into two layers.

(Iii) measure the overall height of standing the sample (and _{h 1).}

(Iv) the height of the separation portion after standing a sample (and _{h 2)} is measured.

(V) Substituting h ₁ and h ₂ into the following formula to calculate the separation ratio.

h ₂ / h ₁ × 100 = (separation ratio)
The separation ratio calculated as described above was determined in four stages. The judgment criteria are as shown in Table 3 below.

(2) Sensory test of feeling of use The feeling of use of the ointment can be examined by evaluating three items of hardness, elongation and uncomfortable feeling. Evaluation is to evaluate whether it is appropriate as a drug for treating hemorrhoids. An ointment is not suitable for a drug for treating hemorrhoids if it is too hard or too soft, and is not suitable for a drug for treating hemorrhoids if it is too stretched or stretched too little. The sensory test is performed by the following procedures by six subjects who do not have hemorrhoid disease.

  (I) About 2 g of each ointment of each of the examples and comparative examples is injected into a part of the subject where a hemorrhoid disease can occur (around the buttocks).

  (Ii) The test subject evaluates each item of 1) hardness, 2) elongation, and 3) uncomfortable feeling of each dispersive hemorrhoid in five stages as a feeling of use. The five-level evaluation is performed from the viewpoint of whether there is a problem when used as a drug for hemorrhoids. Each evaluation item and its degree are as follows.

1) Hardness evaluation item 1 = Dissatisfied 2 = Slightly dissatisfied 3 = None 4 = Slightly satisfied 5 = Satisfactory 2) Elongation evaluation item 1 = Dissatisfied 2 = Slightly dissatisfied 3 = None 4 = Slightly satisfied 5 = Satisfaction 3) Evaluation item for discomfort 1 = Yes 2 = Somewhat 3 = Neither 4 = No almost 5 = No

  Table 5 below shows the results of the separation test and the sensory test on the feeling of use for the dispersion type hemorrhoid treatment ointment of each Example and Comparative Example.

  As is apparent from Table 5, the dispersal hemorrhoid treatment ointment of each example exhibited an excellent feeling of use equivalent to that of the comparative dispersal hemorrhoid treatment ointment, and was much superior to the comparative example. It can be seen that high temperature stability is exhibited.

Claims (12)

Agents, white petrolatum, the oils of microcrystalline wax and liquid state at room temperature a including distributed systems hemorrhoid therapeutic ointments,
A dispersion type hemorrhoid treatment ointment, wherein the room temperature liquid oil is a vegetable oil . The ointment for treating dispersal hemorrhoids according to claim 1, wherein the microcrystalline wax is contained in an amount of 2 to 7% by weight based on the total amount of the ointment. 3. The dispersion type hemorrhoid treatment ointment according to claim 1, wherein the room temperature liquid oil is contained in an amount of 3 to 20% by weight based on the total amount of the ointment. The dispersion type hemorrhoid treatment according to any one of claims 1 to 3, wherein the content of the microcrystalline wax and the room temperature liquid oil is 0.4 to 10 parts by weight with respect to 1 part by weight of the former. Ointment. The dispersal hemorrhoid treatment ointment according to any one of claims 1 to 4, wherein the white petrolatum is contained in an amount of 43 to 93.5% by weight based on the total amount of the ointment. The ointment for treating dispersal hemorrhoids according to any one of claims 1 to 5, wherein the agent is contained in an amount of 1.5 to 30% by weight based on the total amount of the ointment. The dispersal hemorrhoid treatment ointment according to any one of claims 1 to 6, wherein the white petrolatum has a color concentration of 0.5 to 20Y. Examples oils liquid state at room temperature, further liquid paraffin, and Sukuwara emissions or dispersion according to claim 1, characterized in that Ranaru comprising at least one of oils selected from the group hemorrhoids Therapeutic ointment. The ointment for dispersal hemorrhoid treatment according to claim 1 , wherein the vegetable oil is olive oil. The ointment for treating dispersal hemorrhoids according to any one of claims 1 to 9, wherein the agent comprises a drug selected from the group consisting of an anti-inflammatory agent, a local anesthetic, a refreshing agent and an astringent. Agent. The ointment for dispersal hemorrhoid treatment according to claim 10, wherein the anti-inflammatory agent is a steroidal anti-inflammatory agent. The ointment for treatment of dispersal hemorrhoids according to claim 10 or 11, wherein the astringent is zinc oxide.