JP2002322071A - Vespid venom therapy not using vespid sting - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a vespid venom liquid preparation, a method for producing a vespid venom liquid, and a use of the vespid venom liquid, which relate to a vespid venom therapy. SOLUTION: This vespid venom therapy is characterized by having an effect capable of dramatically alleviating the pain and dysphoria of a patient, or the like subjected to a vespid venom treatment, when a vespid venom injection preparation containing the vespid venom and a topical anesthetic is injected to the patent, or the like.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to bee venom therapy, and also relates to bee venom formulation, a method for producing bee venom, and uses thereof.

[0002]

2. Description of the Related Art A method for treating bee products (Apitherap)
y) refers to the medical use of various substances produced by bees, namely honey, pollen, propolis, beeswax, royal jelly and bee venom. Research has shown that honey can be used as an antibacterial, antifungal,
It has been found that it has had antiproliferative and anticancer applications. For example, honey has been used in China as an analgesic and disinfectant for burns. Recently, caffeic acid contained in propolis has a precancerous change when injected with a carcinogen into the colon of rats.
nge). Preparations made from honeycomb strips rich in pollen have not only been successful in treating allergies, but are also used as excellent foods. Here we mainly focus on research on treating painful diseases caused by chronic inflammation using bee venom.

In fact, various forms of bee product treatment have been used since ancient times. Ancient authors: Hesiod (800 BC), Aristophanes (450-388 BC), Baro (166-27 BC),
A wide range of authors, such as Corumella (1st century AD), have described honeycomb culture. Hippocrates (460-377 BC), also called the father of medicine, is used for treatment,
"A very mysterious remedy (Arcanum)." Galan, the father of experimental physiology (131 AD
~ 201) recorded in his collection of medical treatises. Emperor Charmagne (742-814 AD) said he had treated with a bee stinger. Quran 16
Chapter 71 describes the following regarding bee venom: "The liquid of the contents generated from their abdomen becomes medicine for humans. 』

[0004] Scientific understanding of bee product therapy and bees has been described approximately 100 years ago by the Austrian physician Phillip Terc's research paper, The Unique Between Bee Stings and Rheumatism. It began in earnest since the report on correlations was published.

[0005] Today's proponents of bee product treatment suggest that bee venom and other bee products cause chronic pain and many other disorders, ie, regression and inflammation of connective tissues (various types of arthritis). , Neurological diseases (migraine, peripheral neuritis, chronic low back pain), autoimmune diseases (multiple sclerosis, lupus (lupu)
s)) and claims to be efficacious against diseases such as skin disorders (eczema, psoriasis, herpes inflammation). On the contrary, conventional medicine has shown only rare interest in bee products and can be caused by the following two areas that are not related to the above effects: (i) bee sting Anaphylactic shock
(ii) the danger of hypersensitivity reactions, including (i.e., ock) and (ii) the use of bee venom itself as an immunotherapy for allergic reactions manifested by bee stings, especially life-threatening anaphylactic reactions in adults is there.

[0006] Despite promising bee product treatments in the alternative medicine community, the above reasons are also due to the standardized bee venous injection.
It is true that the clinical application of bee venom has been pushed out of the mainstream of medicine and weakened due to lack of ompartations, limited processing procedures for effective use of bee venom, and the like. In addition to the risks described above, bee venom therapy is often painful. Injecting bee venom by stabbing a live bee is dangerous and difficult to control. This method is also not easy for patients to overcome the insects and the disgust of being stung. Even with less painful techniques such as acupuncture, bee venom itself produces some of its own pain, burning and irritating pain. With such a treatment, one must question whether the treatment itself is worse than the disease itself. From the viewpoint described above, there is a need for a formulation of a standardized bee venom and a method of injecting it into patients in need of such treatment. There is a need for a method that reduces the pain of using live bees, especially when treated with bee venom. The present invention is to solve such a problem in earnest.

[0007]

SUMMARY OF THE INVENTION The present invention has been made to solve the above problems, and an object of the present invention is to provide:
It is to provide a standardized bee venom formulation suitable for injection by injection. This bee venom formulation is 1 mL of injection solution
And about 0.1 to about 10 mg of dried bee venom. The formulation also contains a diluent, preservative, buffer, viscosity modifier, co-solvent (co-solven).
Excipients such as t) and its analogs can be included. Preferably, the bee venom formulation provides 0.5 to 5 mg of bee venom in 1 mL of the injection solution.

[0008]

Preferably, the injection of bee venom contains about 0.01 to about 1 mg of melittin and a total protein of about 80 to about 9500.
Contains μg. Most preferably, the bee venom injection contains about 0.04 to about 0.05 mg of melittin in 1 mL of the injection and the total protein is about 800 to about 950 μg.

Preferably, the standardized bee venom injection according to the present invention is filtered for bacteria, bacterial debris, viruses and other contaminants through a 25 μm filter.
The formulations of the present invention are standard injections, intradermal, subcutaneous, muscle, etc., and are pure enough to provide safe and appropriate treatment. It is the purest injection than any other bee venom formulation ever known. Nevertheless, it retains all of the most active components of bee venom and can be obtained by industrially available techniques. Thus, this standard injection offers a unique compromise between safety, efficacy, simplicity, cost and the like.

[0010] Yet another aspect of the present invention is to significantly reduce the pain often associated with bee venom therapy. Usually, bee venom therapy is a treatment in which a small amount of bee venom is injected into several places. For example, 1 mL of dry bee venom per 1 mL of injection
The bee venom containing mg can be injected about 50 times into or around the inflammation. Therefore, a 0.1 mL injection containing about 0.1 mg of dried bee venom will be injected for each injection. Each of the 50 injections is accompanied by swelling and inflammation that appear normally when pierced by a bee sting, as well as pain, burning pain, itching, irritating and irritating pain. From these, these symptoms are collectively described as "irritating irritation". Topical application of conventionally used anesthetics does not reduce or eliminate such unfortunate side effects.
They can slightly reduce the discomfort of piercing the needle, but do not prevent the spread of tingling irritations caused by the injected bee venom.

Therefore, it is completely unexpected to find an anesthetic, especially a local and local anesthetic, that can be injected with bee venom or injected immediately before or immediately after injection at the bee venom injection site. That is. When applied in this manner, local and local anesthetics are usually used at or below 2% when treating bee venom pain, but at much lower concentrations and volumes. Was also found to significantly reduce the irritation associated with bee venom injections. Indeed, 1% to 2% local anesthetics are often applied topically in the clinic, but higher concentrations and volumes are often required during medical procedures where very severe pain is induced. From this point of view, injection 1
It is surprising that the unpleasant symptoms associated with bee venom injections are alleviated even at doses of 2 mg or less per serving. Furthermore, it is a particularly surprising finding that such benefits have been observed when applied only 10 times the bee venom dose.

It is surprising not only that the amount of local anesthetic used in applying such a method is small, but also that it works. Applying such volumes and concentrations of local anesthetics topically or topically only provides an analgesic effect for only a short period of time. These can slightly alleviate the immediate pain upon injection.
However, bee venom injections become very painful about 10 to 15 minutes after injection, and this time is much longer considering the reduction in pain caused by a small amount of local anesthetic.
Again, it was a surprising finding that the application of a local anesthetic as described herein reduced pain for a considerable time after injection. In fact, the pain relief was consistent throughout. In other words, patients do not feel at all that sudden pain becomes more severe even if the local anesthetic gradually disappears 5 to 10 minutes after injection.

Accordingly, the compounds of the present invention include at least one anesthetic in a volume effective for treating bee venom and a volume that reduces the soreness associated with bee venom injection. In a preferred embodiment of the present invention, bee venom and an anesthetic are mixed and administered as a single preparation. However, the compounds according to the invention can also be produced in situ, by first injecting the appropriate amount of anesthetic into the injection site of the patient and then injecting the appropriate amount of bee venom, or in the opposite order. You can also.

Generally, the anesthetic is provided in a ratio of about 20: 1 to 10: 1 by weight of bee venom. The preferred ratio is from 10: 1 to 1:10 by weight. But,
A more preferred ratio of anesthetic to bee venom is from 3: 1 to about 1: 1 by weight. Bee venoms and anesthetics both contain at least one excipient and at least one liquid carrier.
1 mL of the compound of the present invention contains about 0.1 to about 10
The preferred standard bee venom injection, in mg, is as described above.

The present invention also provides a method for administering bee venom. In order to reduce patient discomfort during treatment, a therapeutic amount of bee venom and at least one anesthetic are administered simultaneously or sequentially, as described above. Both are injected intradermally, subcutaneously, or at the same site in muscle (ie, if an anesthetic is injected intradermally at a specific point on the patient's left knee, bee venom is also injected intradermally at the same point). .

The volume of the anesthetic used in these methods is as follows:
The therapeutically effective volume of bee venom is the smallest volume sufficient to reduce the soreness associated with injection. Generally, about 0.01 to about 1.0 mg of bee venom will be infused for each injection tailored to these methods, with a preferred volume of about 0.05 to about 0.5 mg. The most preferred dose is to administer about 0.1 mg per injection. The total dose of bee venom per treatment depends on the number of injections. Similarly, the volume of anesthetic administered is from about 0.01 to about 10 mg per injection, with the preferred volume being from about 0.1 to about 1.
0 mg. The most preferred anesthetic volume is about 0.1 to about 0.3 mg per injection.

Still another aspect of the present invention is a rheumatoid (r)
hematoid) arthritis, osteoarthritis, gout, psoriasis arthritis, ankylosing spondylitis, myalgia, myofibritis, fascia disorder pain syndrome, tennis elbow, golf elbow, fifty shoulder, bursitis (bu
rsitis, tendinitis, chronic surgical inflammation of soft and bone tissue, peripheral neuritis, neuralgia, migraine, eczema, psoriasis, multiple sclerosis, lupus, as well as autoimmunity,
This is a method for treating nervous, cutaneous and degenerative chronic diseases, etc. with the above-mentioned pharmaceutical composition for injectable bee venom.

The above objects and other features and advantages of the present invention will be apparent from the following description of preferred embodiments of the present invention.

[0019]

DETAILED DESCRIPTION OF THE INVENTION The bee venom in the present invention is a bee (A).
pi.mellifera).
The general composition of bee venom is shown in Table 1 below.

[0020]

[Table 1]

The most important component of dried bee venom is a peptide known as Melittin,
Stimulates the pituitary gland and adrenal glands to cortisone (cortisone)
ne) is produced. This is hydrocortisone (hyd
rocortisone) is 100 times more active. Melittin also acts to stabilize lysosomes, cell membranes that protect against inflammation. Another major pharmacological ingredient is apamine (apami).
n), MCD peptide (MCD-peptide: known as peptide 401), adrapine (adola)
and various types of protease inhibitors. Apamin acts like melittin. This is also the complement system (the complement)
system), suppresses the _{C 3} involved in inflammation. MC
D peptide is arachidonic
c) to suppress prostaglandin (prostaglandin)
Landin) prevents synthesis. Adrapine inhibits microsom cyclooxygenase. This is also the case for lipoxygenase.
And thromboxan.
Proteolytic enzyme inhibitors include carrageenan (carrageen).
nin), prostaglandin _{E l,} bradykinin (bradykinin) and inhibiting inflammation caused by histamine. Thus, the term "bee venom" as described herein also refers to administration of medicin, a pharmacologically active component of bee venom, or a combination of melittin and peptide 401. The term “bee venom”
Is, of course, also referred to as a whole bee venom, and is a preparation prepared by purifying the whole bee venom and its components in a pure manner according to the present invention.

While conventional bee venom therapy has utilized live bees, the preferred standard bee venom formulation of the present invention is a mixture with a liquid carrier. Any liquid can dissolve dry bee venom well and can be used in the present invention if it is pharmaceutically suitable for intradermal, subcutaneous or intramuscular injection. The most preferred carrier is water with sterilized ions removed, or 0.9% sodium chloride.
Physiological saline solution. Generally, the liquid carrier according to the present invention contains about 0.1 to about 1 to 1 bee venom per mL.
It is sufficient if it contains 0 mg. More preferred are those containing about 0.5 to about 5 mg of bee venom per mL. Most preferred is an amount such that about 1 mg of bee venom is contained per mL of liquid carrier. For example, 1 g of dry bee venom is added to 1 L (1,000 liters) of normal saline for injection (0.9% sodium chloride)
mL). It is desirably prepared in a sterilized room at room temperature of 20 ° C. As a result, standard bee venom injection 1
Each milliliter contains 1 mg of bee venom.

After passing through a 25 μm filter, a standard bee venom injection preferably contains about 0.01 of melittin in 1 mL.
It contains 1 to about 1.0 mg and the total protein is about 80 to about 9,500 μg. More preferably, the resulting pharmaceutical composition comprises from about 0.01 to about 0.1 mg of melittin per ml and a total protein of from about 400 to about 4.5.
The most preferred standard solution contains 1 μg
Each contains about 0.04 to about 0.05 mg of melittin and about 800 to about 950 μg of total protein. The most preferred standard solution has a hyaluronidase activity of 40 to 1 per mL.
At 00HHU / mL (100 μg / mL diluted), gelatin-induced hemagglutination appears at 3-5 mm / H.

Any purification method that is practical to provide bee venom of the same purity as obtained with a 25 μm filter may be appreciated. Such methods include normal and reverse phase chromatography, affinity chromatography, recrystallization, immunological precipitation, membrane permeation methods and other filtration methods.

In addition to the liquid carrier, the bee venom formulation according to the present invention also comprises another conventional excipient, a viscosity modifier (viscosi
ty modifiers, preservatives and additives such as sodium chloride, sugars and the like. Excipients such as these include, without limitation, benzyl alcohol, methylparaban, Ringer, and other biologically acceptable substances commonly used in injectable therapeutics.

The liquid carrier according to the present invention includes not only physiological saline but also all liquid carriers that can be used for the human body, such as a phosphate buffer (pH 4.0). Also, propylene glycol, which is often used as a solubilizer for injections,
Includes any biologically or pharmaceutically acceptable substance, such as Ethyl Digol.

A typical formulation according to the invention contains 1.0 mg of pure and dry venom of Italian bees and 9.0 mg of sodium chloride per mL of water. Another desirable formulation consists of 1.0 mg of pure and dry bee venom, 9.0 mg of sodium chloride, 0.009 mL of benzyl alcohol and 0.991 mL of water. Again, formulations such as these remove any material larger than 25 μm through a filtration device. It is also intended to use a finer filter than this.

When treating various diseases using bee venom alone, for example, arthritis, multiple sclerosis, alleviation of joint and back pain, multiple injections are usually given. In general, bee venom therapy is usually performed for about 6 to 12 weeks, and is treated once or more once a week, and the number of injections is increased starting from one or two times and thereafter. Will inject 20 to 50 injections per treatment. The dose of bee venom described here is administered from about 0.01 to about 1.0 mg per injection. Preferably, the volume of bee venom is about 0.05 to about 0.5 m per injection
g is best, and the best volume is about 0.1 mg per injection. Thus, 1 mL of the above two prescriptions will provide 10 divided doses of 0.1 mL each containing 0.1 mg of bee venom.

The bee venom injection according to the present invention is usually 0.1%.
Inject intradermally with a syringe with a 25 to 27 gauge needle graduated in mL. Needles generally range in length from about 1/4 to about 5/8 inch. Before treating a patient, it is appropriate to do a skin test to check for possible allergic reactions. Approximately 1/2 of the normal dose on the flexor surface of the forearm etc.
Alternatively, 0.05 mL is slowly injected intradermally to create a hemispherical bleb. Examination of the skin reaction is based on the size of the swelling,
The determination is based on the size of the erythema, the appearance of the irregular spread, and the pseudo-pod projections that appear to the test site. A normal reaction is that a blood spot near the end of the needle is seen where the needle has entered, the swelling is about 0.5 to about 1.0 cm, and the reddish red is about 1 to about 2 round from the injection site.
Appears spreading in inches. If no systemic reaction occurs 15 to 30 minutes after injection, it is considered negative.

When administering intradermally, it is advisable to withdraw the injection plunger slightly prior to injection and to observe blood flowing into the syringe to prevent intravenous injection. The injection will be given to a variety of different sites depending on the affected area of the patient. However, in order to relieve and treat the pain of an arthritic patient, for example, an injection is first made from a painful site. Most preferably, the injection is a tender point or a trigger point.
It is better to inject at er point). Then, to maximize the therapeutic effect, the skin rash condition (derm
A spike site (spina) by an atom chart
l area). Typically,
Avoid drinking alcohol while receiving treatment. If local reaction is severe, apply cold packs (ice packs) or menthol ointment. If itching is very severe, Benadry is used when sleeping.
l) 75 mg may be taken and 50 mg during the day. If mild fever or other chills occur, acetaminophen or other antipyretic may be taken.

The present invention also includes an apparatus for collecting poisons from bees in a refining process using a low volt electric shock method.
This extractor consists of two wooden frames, one inside the other. A number of wires are attached to the front of the outer frame, which alternately ground and charge. If the bees approach and come into contact with the two wires, the circuit will be completed and will eventually impact.

The extractor is placed in front of the honeycomb and connected to a 9 volt battery with an electric timer. When the battery is connected, the current repeatedly flows for 5 seconds and stops for 3 seconds. As soon as the device is turned on, the bees get excited and get out of the beehive and attack the extractor. At the same time, the bees spray the pheromone into the air, causing other bees to excite and attack. When bees receive an electric shock, their lower abdomen bends and their needles pierce the silicone rubber sheet covered on the top of the inner wooden frame. If the current stops for 3 seconds, the bees will not remove the bee needle and die. Pure liquid bee venom accumulates under the silicone rubber sheet. Remove the inner crate from the outer crate and store in a sterile box.

The box is placed in a sterilized refrigerator (4 degrees Celsius) for 4 to 6 hours to dry. Remove the inner crate from the box, place it in a large sterile basket, and scrape dry bee venom crystals with a sterile medical razor. The collected bee venom crystals are placed in a sterile bottle and sealed. Bee venom is disclosed in U.S. Patent Nos. 4,739,531 and 3,16.
It can also be produced by the method described in 3,871.

In treating various diseases,
The use of the standard bee venom injection formulation according to the present invention is described in detail herein and offers significant advantages over the prior art.
However, the experience of being stabbed by a living bee is by no means pleasant. The experience of being stabbed more than 30 times
Naturally, it is to increase the degree of discomfort. The scorching pain experienced by bee venom is unique and unlike any other pain or irritation. Preferably, the injection of the standard formulation according to the invention intradermally is much more pleasant than a bee sting, but the soreness caused by the injection of bee venom should be treated with bee venom therapy. Is hesitating. Accordingly, a preferred embodiment of the present invention provides a composition and method that alleviates, reduces, or even eliminates the unpleasant irritation caused by bee venom injection. This finding is surprising, as scorching, sharp stabbing and other sorenesses occur when bee venom is injected intradermally, even when topical anesthetics are applied, especially local anesthetics. What could not be eliminated was that injecting a local anesthetic with or simultaneously with bee venom at the same point would reduce or eliminate the pain.

Unfortunately, unexpected problems have been discovered with the introduction of local anesthetics in this manner. For example, lidocaine is 2%
If you use the bee venom injection contained (lidocaine 20m
g / mL: 1 mg / mL bee venom), sharp stabbing pains, tingling and other irritating stimuli that occur when injected intradermally are reduced. However, lidocaine itself induces a tingling irrespective of the stimulation of bee venom.
The result is much better than using only bee venom. However, when the volume of local anesthetic exemplified here is injected locally and topically with bee venom, another tingling sensation may occur.

[0036] Much less volume (ie, less than 1%) than the volume of a local anesthetic commonly applied locally or locally
It was an unexpected finding that when injected, it significantly reduced the irritation caused by bee venom while also eliminating the irritating irritation that occurs during intradermal injection of a local anesthetic.

The use of bee venom in the present invention is as described above, or with or without a filter, with or without purification, and also with other bee venoms. Formulations can also be used. The pharmacological composition of interest can also be mixed with a local anesthetic and injected as a single solution into a single syringe. However, bee venom and local anesthetic are made into a single solution and injected,
Alternatively, simultaneous injection is not always necessary. A local anesthetic can be made separately and injected at the same point after bee venom injection. It can also be injected immediately before. For continuous local anesthetic injection, within 1 hour before and after injection of bee venom It is good to be within 10 minutes. Desirably, bee venom and local anesthetic should be injected continuously.
Good within 0 minutes or several minutes after injection. The most desirable method is to inject the local anesthetic immediately before or immediately after the injection of bee venom.

If bee venom is injected into a muscle, a local anesthetic is also injected into the muscle at the same point. It is the same when given subcutaneously, and also when injected intradermally, which is the best method.

The reduction in the irritating irritation associated with bee venom injections is somewhat subjective. This depends on various factors, such as the pain area of the patient's pain; the number of injections; the volume of bee venom injected per injection; the injection site; the depth of the injection following intradermal, subcutaneous, or intramuscular injection. However, it can generally be said that the appropriate amount of local anesthetic described here appears when the same patient applies the same protocol and injects at the same volume than when the same volume is injected without the local anesthetic. The irritating irritation is much reduced.

The local anesthetics according to the present invention include any composition capable of reducing the irritation caused by bee venom injection. The anesthetic is not limited to local and local anesthetics only. However, local anesthetics are preferred. The anesthetic of the present invention is as follows.

Ambucaine, Amoranone, Amylokine Hydrochloride
e), Benoxinate, Benzocaine, Betoxcaine, Bifenamine (Bip
hen amine), bupivacaine (Bupivac)
aine), butacaine, Butamben, butanilicaine (But)
anilicaine), butesamine (Buteth)
amine), butoxycaine (Butoxycai)
ne), Carticaine, chloroprocaine hydrochloride (Chloroprocaine H)
ydrochloride, cocaethylene (Coca)
ethyne), cocaine (Cocaine), cyclomethicaine (Cyclomethaine),
Dibucaine Hydrochloride
loride), Dimethisoquin (Dimethiso)
quin), dimethocaine (Dimethocaine)
e), diperodone hydrochloride (Diperodon Hydror)
ochloride), dyclonine (Dyclonin)
e), econidine (Ecgonine), ecgonine (Ecgonine), ethyl chloride (Ethyl C)
chloride, etidocaine
e), b-Eucaine, euplocin, Efencomine (Fen)
alcohol, Fomokine
e), Hexylcaine hydrochloride (Hexylcaine H)
hydrochloride), hydroxytetracaine, isobutyl p-aminobenzoate (Isobutyl p-Amin)
obenzoate), rosinocaine mesylate (Le
ucinocaine Mesylate, Levoxadrol, Lidocaine (Ll)
docaine), mepivacaine (Mepivacai)
ne), meprilcaine,
Metabutoxycaine
e), methyl chloride (Methyl Chloride)
e), Myrtecaine, Naepaine, Octacaine (Octac)
aine), Orthocaine,
Oxetazaine, paretoxcaine, phenacaine hydrochloride (Phenacaine Hydrochloro)
ride), phenol (Phenol), piperokine (Piperocaine), pyridocaine (Pir)
idocaine), polidocanol (Polidoc)
anol), Pridocanol
1), Pramoxine, Pri cocaine, Procaine (Pro
Cine), propanocaine (Propanocai)
ne), Proparacaine
e), Propipocaine,
Propoxycaine hydrochloride (PropoxycaineHy)
drochloride), pseudo cocaine (Pseud)
ococaine), pyrocaine (Pyrrocaine)
e), Ropivacaine, Salicyl Alcohol,
Tetracaine Hydrochloride
chloride), tricaine (Tolycain)
e), Trimecaine, Zolamine and the like. Among these, the most desirable local anesthetic which meets the present invention is lidocaine.

As can be appreciated, the volume of local anesthetic is controlled by the amount of bee venom used. However, the volume can be adjusted according to the specific condition of the patient, the severity of the pain and the course of treatment. Generally, the volume of local anesthetic is used at a ratio of about 20: 1 to about 1:10 relative to the weight of dry bee venom. A desirable ratio is about 1
0: 1 to about 1: 5 is good, and the most desirable ratio is about 3: 1 to about 1: 1.

The liquid carriers and excipients used in the formulation of a local anesthetic according to the present invention may be the same as or different from those used in making a bee venom formulation. Local anesthetics are also liquids, and prescriptions can be purchased premixed with one or more liquid carriers and excipients. In such a case, no other liquid carrier or excipient is required. In addition, these types of local anesthetic prescriptions may be used as a carrier for bee venom, or may be used in admixture with standard bee venom injections as described above.

The injection amount of the local anesthetic is about 0.0
1 to about 2.0 mg, preferably about 0.05 to about 1.0 mg. The most desirable volume is about 0.1 mg per injection.

A typical formulation is as follows.
(1) Every 1.0 mL of distilled water for injection contains 1.0 mg of dried bee venom of bees, 9.0 mg of sodium chloride, and 1.0 mg of lidocaine hydrochloride. (2) distilled water for injection 1.0
Each mL contained 1.0 mg of dried bee venom of bees, 9.0 mg of sodium chloride, 1.0 mg of lidocaine hydrochloride, 0.009 mL of benzyl alcohol, and 0.991 mL of water.
(3) 1.0m of bee venom dried by 1.0mL of water for injection
g, sodium chloride 9.0 mg, lidocaine hydrochloride 1.0
mg and 0.1 mg of methylparaben.

The present invention also includes creams, ointments and patches containing bee venom in addition to injections. Bee venom cream formulation Dry bee venom 5% (1-25%); Methyl salicylate 4% (1-20%); Purified capsaicin 0.03
% (0.01-0.05%); aloe extract; menthol; caboma 940; cetyl alcohol; methyl paraben; * Directions: 1/16 to 1/8 teaspoon is applied to the affected area. Use 1-2 times a day.

Bee venom patch preparation 10 mg of dried bee venom; 150 m of methyl salicylate
g; purified capsaicin 1 mg; aloe extract; menthol; wit point glyceide; methyl paraben. * Properties: The size of the patch is 100 mm x 1.40 mm, and the above preparation is applied to a nonwoven fabric and the solid surface is covered with a release paper. * Directions: Attach to the affected area one or two times a day, once or twice a day.

EXAMPLES The patients described in the following examples, still treated with conventional modern medicine, still suffer from considerable pain. Taking a number of drugs such as analgesics, muscle relaxants and anti-inflammatory drugs, various injections are also performed, spinal surgery,
Despite receiving physical treatment and sometimes surgery, their morbidity did not improve, and the pain was particularly severe.

The example recorded next used a solution containing bee venom and lidocaine in a 1: 1 ratio for every 0.1 mL of injection from the sixth treatment. 1st to 5th
Up to the second, only pure bee venom was used. The injection solution was prepared by mixing with physiological saline for injection, and purified through a 25 μm filter. Injection 1 for each patient
The batch was injected so as to be 0.1 mL each. The total number of injections depended on the condition of the patient and the number of treatments.

In each example, patients were infused intradermally with a formulation according to the invention and treated twice a week, averaging 12 to 20 treatments. In the next case, "RA Titer" is a blood value often used to diagnose rheumatoid arthritis.

[0051] If the appropriate dose value is less than 20, it is negative, a result strongly desired for such patients. "E
"SR" stands for "red blood cell sedimentation rate" and is generally used to diagnose inflammation. Normal values are 1 to 10. Higher values indicate systemic inflammation.

"ROM" means the range of motion. The specification value of the range of exercise differs depending on the joint in question. However, the greater the distance between the two ends, the greater the range of motion. Tenderness and swelling are indicated by a plus (+) sign on a standard scale. Each plus (+) sign means approximately 20%.

The largest number, 5 plus (+), means the visual similarity ratio between the largest tenderness and "VAS", which means swelling (swelling). Most frequently used buses (VA
In S), the left end of the 100 mm parallel line has no pain, and the right end means the most severe pain so far. The patient should indicate on a 100 mm line how much pain he or she currently feels. Pain intensity is measured by the value up to the point indicated by the patient at the left end.
Such a method is described in “Textbook of Pain” published by Churchill Livingstone (New York, 3rd edition, 199
"Pain Management" (Philadelphia, 2nd issue 1) published by Lee and Feviga, pp. 338-339.
1990, pp. 581-582).

Example 1: Rheumatoid arthritis (Rheu
NG was a 39 year old female patient with rheumatoid arthritis for 19 years. She tried all treatments, including anticancer drugs, but was ineffective. The pain and swelling of her wrists and hands were too severe and unbearable, resulting in her disability. This patient improved by as much as 95% after receiving the treatment according to the invention. The patient's condition was stable and no further pain and swelling appeared.

[0055]

Example 2: Osteoarthritis HR is a 75-year-old woman who has been suffering from degenerative arthritis for the last 25 years. Her knees and spine became worse than other joints. This patient was in very good condition after 18 treatments with the treatment according to the invention. Currently, other drugs are well spent without taking.

[0057]

Example 3: Ankylosing spondylitis MO is a 53-year-old female patient who has been hurting her lower back for a long time and has undergone many operations such as lumbar prosthetic fusion. This patient had no special effect despite receiving rehabilitation treatment for 18 months. This patient received a total of 26 treatments with the treatment according to the invention and has improved significantly. Currently he is not taking any medications but needs to be re-examined at least once a month.

[0059]

Example 4: Muscle pain PA was a 32-year-old girl suffering from muscle pain. Previously, all physical and mental therapies could not be successful. Trigger point injection
injections were injected into several sites for treatment. Total recovery was achieved with a total of 16 treatments. A "trigger point" is a point that causes pain when stimulating a special part of a muscle.

[0061]

Example 5: Tennis Elbow (tennis El)
bow) JK was a 43-year-old boy who had "tennis elbow" for four years. Traditional modern treatments have failed. The treatment of the present invention completely recovered in a total of 12 treatments.

[0063]

Example 6: Adhesive cystitis BO is a 56-year-old male patient who had frozen shoulders.
holder). Taking drugs, various injection treatments, and surgery were also unsuccessful. The patient's range of motion was limited to 20% and complained of persistent pain. The treatment of the present invention completely recovered after a total of 14 treatments.

[0065]

Example 7: Chronic surgical inflammation BC was a 49-year-old male who underwent abdominal surgery 10 times or more for hemorrhagic gastric ulcer, alcoholic cirrhosis, intestinal obstruction and the like. Surgical pain and pain in the gallbladder resulted in severe drug addiction. The treatment of the present invention was almost 100% completely cured after a total of 28 treatments for surgical scars.

[0067]

Example 8: Herpes zoster neuralgia JP was a 78-year-old female patient suffering from herpes zoster. Medical and surgical treatment failed. The patient improved by more than 90% after 16 treatments with the treatment of the present invention. "Blister" means herpes.

[0069]

Example 9 Psoriasis TH is a 28-year-old male patient who has suffered from psoriatic skin disease for 7 years. Modern medical drugs only helped temporarily. His condition was getting worse and worse, he could not wear short pants even in the sultry summer. A total improvement of 24 treatments has greatly improved. The patient will need to be reviewed at least once a month.

Example 10: Multiple sclerosis SR is a 47-year-old female patient who has been suffering from multiple sclerosis for 15 years. The mobilization of all modern therapies did not prevent the disease from getting worse. She continued to have numbness in her lower extremities, lost about 40% of her urinary control, had weakened limbs, became less balanced, and had to rely on tweezers and quadrupeds. . With a total of 28 treatments, the patient's condition was greatly improved. Now, urination can be adjusted 100%, eliminating the need to use shoes and walkers. This patient will be required to be re-examined at least once every 3 to 4 weeks for a considerable period.

[0072]

Example 11: Pain The ten patients listed in the above example were combined for a total of 30 patients.
Some patients were treated with only an appropriate volume of bee venom up to the first five treatments. Thereafter, that is, from the sixth injection, as described in the "Example", which is summarized along each of the acronyms described above, an injection solution in which bee venom and lidocaine were mixed at a ratio of 1: 1 was injected. The patients were asked about the type of pain, its intensity, discomfort, etc. after each treatment without informing the patients of the injection of the prescribed formulation. In addition, the patient's body language for bee venom injection, degree of frowning, and degree of reluctance to receive treatment were observed.

97% of patients objectively reported that the injection containing bee venom and lidocaine significantly reduced pain and discomfort upon injection. Fear of the next injection was also considerably reduced, and the dropouts dropped dramatically during this treatment. Pain relaxation lasts for a considerable time, and very small amounts of local anesthetic only give the pain relief momentarily, and after a short time the pain suddenly increases. No increase was experienced.

[0075]

As can be seen from the above embodiments, the present invention is intended to reduce the pain and discomfort of patients receiving bee venom treatment by injecting a bee venom injection containing a mixture of bee venom and a local anesthetic. It has a dramatic relaxation effect.

Although the present invention has been described in detail with reference to the embodiments, the present invention is not limited to the embodiments, and the spirit and spirit of the present invention may be modified by those having ordinary knowledge in the technical field to which the present invention belongs. The invention could be modified or changed without departing.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 17/06 A61P 17/06 25/02 25/02 25/06 25/06 29/00 101 29/00 101 43/00 43/00 (72) Inventor Christopher M. Kim New Jersey 07701 Broad Street Red Bank 252 F-term (reference) 4C076 AA08 AA72 BB15 BB16 BB31 CC01 CC18 CC20 CC50 DD37 DD41 DD46 DD52 EE09 EE58 FF16 4C087 AA01 AA02 BB22 CA03 MA05 MA28 MA32 MA63 MA66 NA07 ZA01 ZA08 ZA89 ZB11 ZB15 4C206 AA01 AA02 BA05 GA19 GA31 KA01 MA03 MA05 MA37 MA48 MA52 MA83 MA86 NA07 NA08 ZA01 ZA08 ZB11 ZB15

Claims (10)

[Claims] 1. A pain (irritating irritation) caused by an injection of bee venom and an amount of bee venom capable of expecting a therapeutic effect.
A bee venom injection formulated to be able to simultaneously or sequentially administer a sufficient amount of a local anesthetic to reduce bleeding. 2. The bee venom injection according to claim 1, wherein the local anesthetic is lidocaine hydrochloride, and the bee venom injection has passed through a 25 μm filter. 3. The weight ratio of bee venom to local anesthetic is 10:
The bee venom injection solution according to claim 1 or 2, wherein the ratio is from 1 to 1: 5. 4. The ratio of bee venom to local anesthetic is 3: 1 by weight.
The bee venom injection according to claim 3, wherein the ratio is from 1 to 1. 5. A liquid carrier is contained so as to provide 0.1 to 10 mg of bee venom per 1 mL of bee venom injection solution for preparing a bee venom injection solution.
The bee venom injection according to the above. 6. The bee venom injection according to claim 5, wherein a liquid carrier is contained so as to provide 0.5 to 5 mg of bee venom per 1 mL of the bee venom injection solution for preparing the bee venom injection solution. Agent. 7. The bee venom injection according to claim 6, wherein a liquid carrier is contained so as to provide 1 mg of bee venom per 1 mL of bee venom injection for formulating a bee venom injection. 8. The bee venom injection solution is rheumatoid (Rhe
umatoid) arthritis, osteoarthritis, gout, psoriatic arthritis, ankylosing spondylitis, myalgia, myofiberitis, fascia disorder pain syndrome, tennis elbow, golf elbow, fifty shoulder, bursitis (bur)
sitis), tendonitis, chronic surgical inflammation of soft and bone tissues, peripheral neuritis, neuralgia, migraine, eczema, psoriasis, multiple sclerosis, lupus The bee venom injection solution according to claim 1 or 2. 9. A bee venom cream formulation having the following composition: dry bee venom 1-25%; methyl salicylate 1-20
Purified capsaicin 0.01-0.05%; Aloe extract; Menthol; Caboma 940; Cetyl alcohol; Methylparaben; Fragrance; Wax; Purified water. 10. A bee venom patch formulation having the following composition: dry bee venom 1 to 25%; methyl salicylate 1 to 15
%; Purified capsaicin 0.01-1%; aloe extract; menthol; wit point glyceride; methyl paraben.