WO2006112038A1

WO2006112038A1 - Dispersion ointment for treatment of hemorrhoids excellent in feeling after application and stability at high temperatures

Info

Publication number: WO2006112038A1
Application number: PCT/JP2005/009624
Authority: WO
Inventors: Shirou Tajima
Original assignee: Kobayashi Pharmaceutical Co., Ltd.
Priority date: 2005-03-31
Filing date: 2005-05-26
Publication date: 2006-10-26
Also published as: JP4863641B2; JP2006282559A

Abstract

[PROBLEMS] To provide a dispersion ointment for use in the treatment of hemorrhoids which is excellent in feeling during or after application and stability at high temperatures. [MEANS FOR SOLVING PROBLEMS] The ointment comprises a therapeutic agent, white petrolatum, microcrystalline wax and an oil which is in liquid form at ordinary temperature.

Description

Specification

Ointment for dispersal hemorrhoids with excellent usability and high temperature stability

Technical field

[0001] The present invention relates to a dispersion type hemorrhoid treatment ointment having excellent usability and high-temperature stability.

Background art

[0002] Manic disease is a symptom that occurs in the anal region. Since the affected area of the epilepsy is located in the lower part of the body and always faces downward, ointments and suppositories that are easily applied to the affected area are widely used as external preparations.

[0003] While acting, 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. Problems such as inability to stay, removal of drugs when excreted, and uncomfortable feeling when administered. These are problems specific to gonorrhea.

[0004] Therefore, in particular, it is necessary for an ointment for treating hemorrhoids to dissolve and spread quickly after being applied or immediately administered. Therefore, these ointments are designed to dissolve at body temperature. However, the conventional ointment becomes very unstable at high temperatures, and each component repeatedly dissolves and solidifies before use, resulting in a non-uniformly mixed state. On the other hand, when trying to ensure uniformity, there was a problem that the feeling of use deteriorated because the ointment became too hard. Disclosure of the invention

Problems to be solved by the invention

[0005] An object of the present invention is to provide a dispersion type hemorrhoid treatment ointment having excellent usability and high-temperature stability.

Means for solving the problem

[0006] The present inventors have conducted intensive research in view of the above-mentioned problems, and as a result, by using a combination of a drug, white petrolatum, mic mouth crystallin wax, and room temperature liquid oil, uniformity can be maintained even in a high temperature region. It was discovered that an ointment for treating hemorrhoids with good usability can be prepared, and the present invention has been completed. That is, the present invention provides the following items:

Item 1. An ointment for dispersal hemorrhoids characterized by containing a drug, white petrolatum, microcrystalline wax, and oil at room temperature;

Item 2. The dispersion type hemorrhoid treatment ointment according to Item 1, comprising 2 to 7% by weight of the microcrystalline wax with respect to the total amount of the ointment;

Item 3. The dispersion type hemorrhoid treatment ointment according to Item 1 or 2, which comprises the room temperature liquid oil in an amount of 3 to 20% by weight based on the total amount of the ointment.

Item 4. The dispersion according to any one of Items 1 to 3, wherein the content ratio of the microcrystalline wax and the liquid oil at room temperature is 0.4 parts by weight of the latter with respect to 1 part by weight of the former and LO parts by weight. Ointment for treatment of hemorrhoids;

Item 5. The ointment for treating dispersal hemorrhoids according to any one of Items 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.

Item 6. 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. The ointment for dispersal hemorrhoid treatment according to any one of Items 1 to 6, wherein the white petrolatum has a color concentration of 0.5 to 20Y;

Item 8. The dispersion system according to any one of Items 1 to 7, wherein the oil at room temperature includes at least one oil selected from the group consisting of liquid paraffin, squalane and vegetable oil. Therapeutic ointment;

Item 9. The dispersion type hemorrhoid treatment ointment according to Item 8, wherein the vegetable oil is olive oil;

Item 10. The dispersal hemorrhoid treatment according to any one of Items 1 to 9, wherein the drug includes a drug selected from the group consisting of an anti-inflammatory agent, a local anesthetic, a cooling agent, and an astringent. Ointment;

Item 11. The dispersion type hemorrhoid treatment ointment according to Item 10, wherein the anti-inflammatory agent is a steroidal anti-inflammatory agent;

Item 12. The ointment for dispersal hemorrhoid treatment according to Item 10 or 11, wherein the astringent is acid zinc. [0008] The present invention is described in detail below.

[0009] Examples of the drug that can be incorporated into the ointment for treatment of dispersal hemorrhoids of the present invention include drugs that improve symptoms associated with hemorrhoids, such as anti-inflammatory agents, local anesthetics, refreshing agents, and astringents. It is not limited to it. These drugs can be used alone or in combination of two or more.

[0010] The anti-inflammatory agent may be a steroidal anti-inflammatory agent or a non-steroidal anti-inflammatory agent.

[0011] Steroidal anti-inflammatory agents include dexamethasone, triamcinolone acetonide, beclomethasone propionate, hydrocortisone succinate, methyl succinate, predo-zolone acetate, dexamethasone acetate, hydrocortisone acetate, prednisolone acetate, dexamethasone metasulfone Acid benzoic acid, triamcinolone diacetate, prednisolone butyl acetate, dexamethasone phosphate, hydrocortisone phosphate, prednisolone phosphate, betamethasone phosphate, prednisolone succinate, cortisone acetate, parameterzone acetate, methylprednisolone acetate, triamcinolone, hydrocortisone, prednisolone Betamethasone, prednisolone valerate acetate, diflucortron valerate, dexamethasone valerate, betamethasone valerate, diflupret acetate Donato, diflorazone acetate, difluprednate, betamethasone dipropionate, flumethasone pivalate, fluocinode, fluocinoloneacetonide, alcromethasone propionate, beclomethasone propionate, clobetasone butyrate, hydrocortisone butyrate, hydrocortisone butyrate propionate hydrocortisone Force including, but not limited to, fludocortisone acetate, dexamethasone palmitate, methylprednisolone, and the like. Among the above-mentioned steroidal anti-inflammatory agents, those preferable as a therapeutic agent for hemorrhoids include prednisolone, pred-zolone acetate, hydrocortisone, and hydrocortisone acetate. These steroid anti-inflammatory agents can be used singly or in combination of two or more.

[0012] Non-steroidal anti-inflammatory agents include indomethacin, ibuprofen, ibuprofen piconol, ufenamate, glycyrrhetinic acid, crotamiton, spirophen, glycyrrhizic acid, diclofenac sodium, sulindac, flurbiprofen, salts or derivatives thereof, etc. There is no limitation to these forces. These non-steroidal anti-inflammatory agents can be used singly or in combination of two or more.

[0013] Local anesthetics include lidocaine, pro-power-in, ethyl aminobenzoate, dibu-power-in, Forces including viva force-in, salts or derivatives thereof, and the like, but are not limited thereto. These local anesthetics can be used singly or in combination of two or more.

[0014] Astringents include, but are not limited to, zinc oxide, tannic acid, aluminum sulfate, aluminum sulfate strong lithium, 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 admixture of two or more.

[0015] As a refreshing agent, menthol (1 menthol, dl-menthol), camphor (dl-forced nuffle, d camphor), borneol (d borneol, rhino), gera-all, cineol, linalool, limonene, menthone , Carvone, anethole, methyl salicylate, cinnamic aldehyde, octyl aldehyde, linalyl acetate, menthyl acetate, vinylene, menthyl lactate, eucalyptus oil, bergamot oil, Wikiu oil, rose oil, hearth oil, peppermint oil, spearmint oil, Dipterocarpus essential oil, rosmarin oil, lavender oil, mastic oil, parsley oil, anise oil, eucalyptus oil, wintergreen oil, power shea oil, lemon oil, orange oil, cardamom oil, coriander oil, mandarin oil, lime Oil, laurel oil Chamomile oil, caraway oil, Beiyu, lemon grass oil, pine - one US dollar oil, neroli oil, and jasmine oil, and the like, without limitation. These refrigerants can be used alone or in combination of two or more.

[0016] The white petrolatum that can be blended in the dispersion type hemorrhoid treatment ointment of the present invention is not limited to these, which can be used with a color strength of about 0.5Y to 20Y. The white petrolatum that can be blended in the dispersal ointment ointment of the present invention has a color strength of preferably about 1.3 to 20%, more preferably about 1.8 to 20%. These white petrolatums can be used alone or in admixture of two or more.

[0017] The room temperature liquid oil that can be blended in the dispersion type hemorrhoid treatment ointment of the present invention should be liquid at a temperature of about 25 ° C.

[0018] Examples of such room temperature liquid oils include, but are not limited to, hydrocarbons, vegetable oils, and the like. These room temperature liquid oils can be used singly or in combination of two or more. [0019] The 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 hydrocarbons described above, liquid paraffin, light liquid paraffin, squalene, and squalene are preferred for use as anti-epileptic drugs. These hydrocarbons can be used singly or in combination of two or more.

[0020] Examples of vegetable oils include olive oil, soybean oil, peanut oil, bevana oil, nuka oil, sesame oil.

, Power including, but not limited to, camellia oil, corn oil, menji 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.

[0021] 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 5-25% by weight, more preferably about 7-20% by weight. If the drug content is too high, there will be safety issues, and if it is too low, the effect as a hemorrhoid treatment will be reduced.

[0022] The content of the white petrolatum in a distributed system hemorrhoid therapeutic ointment of the present invention is generally about 43 to 93.5 weight ^_0/0, preferably from about 45 to 85 weight ^_0/0, more preferably about 60 80 is a weight ^_0/0. If the content of white petrolatum is too large, the dispersion ointment for treating hemorrhoids becomes soft, and if it is too small, it becomes hard.

[0023] 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, more preferably about 2 to 4% by weight. It is. 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 temperature is deteriorated.

[0024] 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 stickiness of the dispersal ointment becomes worse, and if it is too low, the elongation becomes worse.

[0025] 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, preferably about 1.5 to: LO parts by weight, more preferably about 2.5 to 7 parts by weight You can. By setting the content ratio of the microcrystalline wax and the room temperature liquid oil within the above range, an ointment with better high-temperature stability and usability can be prepared.

[0026] Further, the dispersal hemorrhoid ointment of the present invention includes, as an optional component, a tissue activator, a fragrance, a colorant, a warm sensation, a thermal component, extracts, as long as there is no problem in use stability. surfactants, solvents, solubilizers, _P H adjusting agents, buffering agents, bases, Shotsutsumizai, emulsifiers, suspending agents, softeners, viscous agents, dispersing agents, excipients, lubricants, antioxidants An appropriate amount of a preservative, preservative, preservative, plasticizer, etc. may be added.

[0027] The total amount of white petrolatum and microcrystalline wax in the dispersion type hemorrhoid treatment ointment of the present invention is preferably more than about 50% by weight, more preferably about 60% by weight or more. is there. High total content increases stability of dispersal ointment

[0028] The dispersal 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 in preparation, such as temperature, order of addition of each component, mixing time, etc., are easily based on the common general technical knowledge in the field, depending on the physical or chemical properties of each component, concentration, equipment capability, etc. Can be selected. In this case, the separation can be further suppressed by mixing the components while degassing under reduced pressure.

The invention's effect

[0029] According to the present invention, it is possible to provide an ointment for dispersal hemorrhoids excellent in both feeling of use and stability at high temperature. That is, the dispersal hemorrhoid treatment ointment of the present invention has an excellent feeling of use, and its fluidity increases at high temperatures, but when it resolidifies at room temperature, the ingredients solidify in a uniform state! Have.

Example

[0030] mmm

Dispersed hemorrhoid treatment ointments of the present invention were prepared by mixing drugs such as zinc oxide and lidocaine, white petrolatum, microcrystalline wax (MK tuss) and room temperature liquid oils (Examples 1 to 16). . Also, instead of microcrystalline wax (MK wax) A dispersion type hemorrhoid treatment ointment was prepared using beeswax and carnal barrow and used as a comparative example. The compositions of the dispersion type hemorrhoid treatment ointment in the examples and comparative examples are as shown in Table 1 below.

[table 1]

Petrolatum 13 shows white petrolatum with different degrees of purification. The color density is used as an index. Table 2 below shows the color concentration and product name of white petrolatum used.

[0033] [Table 2]

[0034] 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.

[0035] (1) Separation test

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

[Ii] (ii) The screw tube is allowed to stand at 50 ° CZ for 7 days. During standing, some of each ointment separates into two layers.

[0037] (iii) Measure the overall height (referred to as h) of the sample after standing.

[0038] (iv) After standing, measure the height (referred to as h) of the separated portion of the sample.

2

[0039] (v) Substituting h and h into the following equation to calculate the separation ratio.

1 2

[0040] h / h X 100 = (separation ratio)

twenty one

The separation ratio calculated as described above was determined in four stages. The judgment criteria are as shown in Table 3 below.

[0041] [Table 3] Determination of separation ratio

0% or more and less than 16% ◎

16% or more and less than 31% O

31% to less than 46% Δ

46% or more X [0042] (2)) ¾ of

The feeling of use of the ointment can be examined by evaluating three items: hardness, elongation and uncomfortable feeling. Evaluation is to evaluate whether it is appropriate as a drug for treating hemorrhoids. An ointment is not suitable as a drug for treating hemorrhoids, whether it is too hard or too soft, and is not suitable as a drug for treating hemorrhoids if it is too stretched or stretched too little. The sensory test is performed by the following procedure for 6 subjects who do not have hemorrhoid disease.

[0043] (i) Approximately 2 g of the ointment of each of the examples and comparative examples is injected into the part of the subject where the hemorrhoids can occur (around the buttocks).

[0044] (ii) Each subject evaluates each item of 1) hardness, 2) extension, and 3) discomfort for each dispersal hemorrhoid treatment as a judgment of the 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.

[0045] 1) Hardness evaluation item

1 = Dissatisfied 2 = Slightly dissatisfied 3 = Neither 4 = Slightly satisfied 5 = Satisfied

2) Evaluation items for elongation

3) Evaluation items for discomfort

1 = Yes 2 = Somewhat 3 = Neither 4 = Almost 5 = No

[0046] [Table 4]

[0047] 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.

[0048] [Table 5] Separation Judgment Use S Separation Judgment Usability Hardness Extension Discomfort Hardness Extension Discomfort Example 1 ◎ 〇〇〇 Comparative Example 1 厶 ◎ ◎ ◎ Example 2 ◎ ◎ ◎ ◎ Comparative Example 2 X ◎ ◎ ◎ Example 3 ◎ ◎ ◎ ◎ Comparative Example 3 X ◎ ◎ ◎ Example 4 ◎ o ◎ ◎ Comparative Example 4 Δ 〇〇〇 Example 5 ◎ ◎ ◎ ◎ Comparative Example 5 X 厶 ◎ 〇 Example 6 o ◎ ◎ ◎

Example 7 ◎ ◎ ◎ ◎

Example 8 ◎ ◎ ◎ ◎

Example 9 o ◎ ◎ ◎

Example 1 0 ○ ◎ ◎ ◎

Example 1 1 ◎ 厶 △ o

Example 1 2 ◎ ◎ ◎ ◎

Example 1 3 ◎ 〇〇〇

Example 14 ◎ ○ o ○

Example 1 5 ◎ 厶 Δ Δ

Example 1 6 ◎ ◎ ◎ ◎ As is clear from Table 5, the dispersion type hemorrhoid treatment ointment of each example showed an excellent feeling of use equivalent to the dispersion type hemorrhoid treatment ointment of Comparative Example, and It can be seen that the high temperature stability is much better than the comparative example.

Claims

The scope of the claims

[I] A dispersion type hemorrhoid treatment ointment comprising a drug, white petrolatum, microcrystalline wax, and room temperature liquid oil.

[2] The dispersion type hemorrhoid treatment ointment according to [1], comprising 2 to 7% by weight of the microcrystalline wax based on the total amount of the ointment.

[3] The dispersion type hemorrhoid treatment ointment according to [1] or [2], comprising 3 to 20% by weight of the room temperature liquid oil based on the total amount of the ointment.

[4] The dispersion 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 for treatment of hemorrhoids.

[5] The dispersal hemorrhoid treatment ointment according to any one of [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.

6. 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.

7. The ointment for treating dispersal hemorrhoids according to any one of claims 1 to 6, wherein the white petrolatum has a color concentration of 0.5 to 20Y.

[8] The dispersion system according to any one of claims 1 to 7, wherein the room temperature liquid oil includes at least one oil selected from the group consisting of liquid paraffin, squalane and vegetable oil. Ointment for treatment of hemorrhoids.

[9] The dispersion type hemorrhoid treatment ointment according to [8], wherein the vegetable oil is olive oil.

[10] The dispersal hemorrhoid according to any one of claims 1 to 9, wherein the drug includes a drug selected from the group consisting of an anti-inflammatory agent, a local anesthetic, a cooling agent, and an astringent. A therapeutic ointment.

[II] The ointment for dispersal hemorrhoid treatment according to claim 10, wherein the anti-inflammatory agent is a steroidal anti-inflammatory agent.

12. The ointment for treating dispersal hemorrhoids according to claim 10 or 11, wherein the astringent is zinc oxide.